Difference between revisions of "Timeline of vitamin D"

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This is a '''timeline of {{w|vitamin D}}'''.
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This is a '''timeline of {{w|vitamin D}}''', attempting to describe significant and illustrative events in the history of vitamin D.
  
 
== Sample questions ==
 
== Sample questions ==
  
 
The following are some interesting questions that can be answered by reading this timeline:  
 
The following are some interesting questions that can be answered by reading this timeline:  
 +
 +
* What are some important events preceeding the discovery of vitamin D?
 +
**  Sort the full timeline by "Event type" and look for the group of rows with value "Prelude".
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** You will see some important events related to the history of vitamin D, like the first description of {{w|rickets}}, and early treatments involving vitamin D, such as {{w|cod liver oil}}.
 +
* What are some health conditions related to vitamin D named in this timeline?
 +
** Sort the full timeline by "Related health condition (when applicable)".
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** You will see a range of conditions, often {{w|rickets}}, but also {{w|cancer}} and {{w|kidney disease}}, among others.
 +
* What are some significant or illustrative studies being conducted on Vitamin D?
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** Sort the full timeline by "Event type" and look for the group of rows with value "Research".
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** You will see a variety of studies of different types, from [[w:Cohort study|cohort studies]] indicating the effect of vitamin D in subjects, to laboratory studies such as molecular cloning.
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* What are some Vitamin D recommended intakes published by competent institutions?
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**  Sort the full timeline by "Event type" and look for the group of rows with value "Recommendation".
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** Check table of recommendations for vitamin D for adults in Canada and United States.
 +
* What are some vitamin D-related drugs having been launched to the market?
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**  Sort the full timeline by "Event type" and look for the group of rows with value "Drug launch".
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** You will see a list of marketed analogs of vitamin D.
 +
* What are some illustrative books specializing in vitamin D?
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** Sort the full timeline by "Event type" and look for the group of rows with value "Literature".
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** You will see a number of publications, some by notable authors such as {{w|Michael F. Holick}}.
  
 
==Big picture==
 
==Big picture==
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! Time period !! Development summary !! More details
 
! Time period !! Development summary !! More details
 
|-
 
|-
| 19th century || || The modern history of vitamin D begins in the mid-century, when it is noticed that city children are more likely to have rickets than rural children.<ref name="Mohrv"/>
+
| Before 1770 || Pre–modern history of vitamin D || {{w|Rickets}}, a condition caused by {{w|vitamin D deficiency}}, is already described as early as in the 2nd century AD. The disease is first identified as a rare disorder in the 1600s, when most people live rural lives with abundant sun exposure.
|-
 
| 1920s || Discovery || Vitamin D is discovered during research into the causes and treatment of {{w|rickets}}.<ref name="Litonjua"/><ref name="milnde"/>
 
|-
 
| 1940s || || The United States and Canada start setting dietary intake recommendations for nutrients.
 
|-
 
| 1950s || || "fear of vitamin D intoxication that was evident in Europe in the 1950s (70) and should be re-evaluated, for they do not reflect our present scientific knowledge” <ref name="Holimicf"/>
 
 
|-
 
|-
| 1960s || || ". Scientists did not have the tools to follow vitamin D metabolism in living subjects until the advent, in the mid-1960s, of new techniques using radioactively labeled substances"<ref name="Hochberg"/> ". In the 1960s, it was clearly demonstrated the vitamin D was a pro-hormone, and that it needed to undergo several stepwise conversions in the body, fi rstly in the skin, then in the circulating plasma, the liver, and fi nally in the kidney"<ref name="Torres"/>
+
| 1770–1920 || {{w|Cod liver oil}} as major vitamin D source || {{w|Cod liver oil}}, rich in {{w|vitamin D}}, is first advocated for the treatment of a disease ({{w|tuberculosis}}). In the late 1700s rickets becomes rampant in Europe as people begin to stay indoors and live in large, polluted cities, with reduced exposure to sunlight. {{w|Cod liver oil}} is first prescribed in 1824 for the treatment of rickets. The modern history of vitamin D begins in the mid-19th century, when it is noticed that city children are more likely to have rickets than rural children.<ref name="Mohrv"/>
 
|-
 
|-
 +
| 1920 onwards || Post–vitamin D discovery era || Vitamin D is discovered during research into the causes and treatment of {{w|rickets}}.<ref name="Litonjua"/><ref name="milnde">{{cite book |last1=Milne |first1=G. W. A. |last2=Delander |first2=M. |title=Vitamin D Handbook: Structures, Synonyms, and Properties |date=2008 |publisher=John Wiley & Sons |isbn=978-0-470-13983-7 |url=https://books.google.com.ar/books?id=RG4yX1Y1IdwC&printsec=frontcover&dq=Vitamin+D+Handbook&hl=en&sa=X&redir_esc=y#v=onepage&q=Vitamin%20D%20Handbook&f=false |access-date=31 August 2021 |language=en}}</ref> The essential role of vitamin D in mineral homeostasis and skeletal health is recognized since the 1930s, when vitamin D fortification of milk eradicates rickets.<ref name="Holimicf">{{cite web |last1=Holick |first1=Michael F. |title=Vitamin D: Physiology, Molecular Biology, and Clinical Applications |url=https://books.google.com.ar/books?id=EhX2sgEACAAJ&dq=vitamin+e+michael&hl=en&sa=X&redir_esc=y |publisher=Humana Press |access-date=16 August 2021 |language=en |date=23 April 2010}}</ref> vitamin D<sub>2</sub> starts being used as a dietary supplement in lieu of vitamin D<sub>3</sub>.<ref name="Holimicf"/> In the 1940s, the United States and Canada start setting dietary intake recommendations for nutrients. In the 1960s, it is clearly demonstrated the vitamin D is a pro-hormone, and that it needs to undergo several stepwise conversions in the body, firstly in the skin, then in the circulating plasma, the liver, and finally in the kidney.<ref name="Torres"/>
 
|}
 
|}
  
 
== Numerical and visual data  ==
 
== Numerical and visual data  ==
 +
 +
The table below shows recommendations for vitamin D for adults in Canada and United States from 1968 to 1997.<ref>{{cite journal |last1=Whiting |first1=Susan J. |last2=Calvo |first2=Mona S. |title=Dietary Recommendations for Vitamin D: a Critical Need for Functional End Points to Establish an Estimated Average Requirement |journal=The Journal of Nutrition |date=1 February 2005 |volume=135 |issue=2 |pages=304–309 |doi=10.1093/jn/135.2.304}}</ref>
  
 
{| class="sortable wikitable"
 
{| class="sortable wikitable"
 
! Country and date
 
! Country and date
! Age groupings
+
! Age groupings (years)
! Recommended value
+
! Recommended value (μg (IU))
|-
 
| || y || ug (IU)  
 
 
|-
 
|-
 
| United States || ||  
 
| United States || ||  
Line 61: Line 75:
 
| Canada || ||     
 
| Canada || ||     
 
|-
 
|-
| 1964 || "Adult" || Nonve given     
+
| 1964 || "Adult" || None given     
 
|-
 
|-
 
| 1975 || 19-35 || 2.5 (100)     
 
| 1975 || 19-35 || 2.5 (100)     
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|}
 
|}
  
Trend of “Vitamin d deficiency” reports<ref>{{cite web |title=Vitamin d deficiency: treatments, associated drugs and conditions (21,591 reports) - eHealthMe |url=https://www.ehealthme.com/condition/vitamin-d-deficiency/ |website=www.ehealthme.com |access-date=13 September 2021}}</ref>  
+
 
 +
 
 +
Trend of “Vitamin d deficiency” reports.<ref>{{cite web |title=Vitamin d deficiency: treatments, associated drugs and conditions (21,591 reports) - eHealthMe |url=https://www.ehealthme.com/condition/vitamin-d-deficiency/ |website=www.ehealthme.com |access-date=13 September 2021}}</ref>  
  
 
{| class="sortable wikitable"
 
{| class="sortable wikitable"
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| 2019 || 2,569     
 
| 2019 || 2,569     
 
|-
 
|-
| 2020 || 2,868
+
| 2020 || 2,868
 +
|-
 +
|}
 +
 
 +
[[File:Vitamin D grfok.png|thumb|center|700px]]
 +
 
 +
=== Google Scholar ===
 +
 
 +
The following table summarizes per-year mentions on Google Scholar as of September 19, 2021.
 +
 
 +
{| class="sortable wikitable"
 +
! Year
 +
! "vitamin D"
 +
|-
 +
| 1920 || 16
 +
|-
 +
| 1930 || 502
 +
|-
 +
| 1940 || 723
 +
|-
 +
| 1950 || 932
 +
|-
 +
| 1960 || 950
 +
|-
 +
| 1970 || 1,780
 
|-
 
|-
| 2021 || 19 
+
| 1980 || 3,350
 +
|-
 +
| 1990 || 4,350
 +
|-
 +
| 2000 || 9,600
 +
|-
 +
| 2010 || 30,000
 +
|-
 +
| 2020 || 45,300
 
|-
 
|-
 
|}
 
|}
  
[[File:Vitamin d.png|thumb|center|700px]]
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[[File:Vitamin D gsh.png|thumb|center|700px]]
  
 
=== Google Trends  ===
 
=== Google Trends  ===
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[[File:Vitamin D gt.png|thumb|center|600px]]
 
[[File:Vitamin D gt.png|thumb|center|600px]]
 +
 +
=== Google Ngram Viewer  ===
 +
 +
The comparative chart below shows {{w|Google Ngram Viewer}} data for vitamin D, vitamin A, vitamin B and vitamin C, from 1900 to 2019.<ref>{{cite web |title=vitamin D, vitamin A, vitamin B and vitamin C |url=https://books.google.com/ngrams/graph?content=vitamin+D%2Cvitamin+A%2Cvitamin+B%2Cvitamin+C&year_start=1900&year_end=2019&corpus=26&smoothing=3&direct_url=t1%3B%2Cvitamin%20D%3B%2Cc0%3B.t1%3B%2Cvitamin%20A%3B%2Cc0%3B.t1%3B%2Cvitamin%20B%3B%2Cc0%3B.t1%3B%2Cvitamin%20C%3B%2Cc0 |website=books.google.com |access-date=19 September 2021 |language=en}}</ref>
 +
 +
[[File:Vitamin D ngram.png|thumb|center|700px]]
  
 
=== Wikipedia Views  ===
 
=== Wikipedia Views  ===
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! Year !! Related health condition (when applicable) !! Event type !! Details !! Location/researcher affiliation
 
! Year !! Related health condition (when applicable) !! Event type !! Details !! Location/researcher affiliation
 
|-
 
|-
| 2nd century AD || {{w|Rickets}} || || Soranus of Ephesus’s describes rickets in Roman children.<ref name="Hochberg"/> ||
+
| 2nd century AD || {{w|Rickets}} || Prelude || {{w|Rickets}}, the bone disease caused by {{w|vitamin D deficiency}}, is described by Soranus of Ephesus’s in Roman children.<ref name="Hochberg"/> ||  
|-
 
| 1650 || {{w|Rickets}} || || {{w|Rickets}}, the bone disease caused by vitamin D deficiency, is described in detail by British physician {{w|Francis Glisson}}.<ref name="Wolfv">{{cite journal |last1=Wolf |first1=George |title=The Discovery of Vitamin D: The Contribution of Adolf Windaus |journal=The Journal of Nutrition |date=1 October 2004 |volume=134 |issue=6 |pages=1299–1302 |doi=10.1093/jn/134.6.1299}}</ref>
 
|-
 
| 1770 || || || {{w|Cod liver oil}}, rich in {{w|vitamin D}}, is first advocated for the treatment of {{w|tuberculosis}}.<ref>{{cite web |title=Cod Liver Oil - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cod-liver-oil |website=www.sciencedirect.com |access-date=11 August 2021}}</ref> Derived from [[w:liver (food)|liver]] of [[w:cod|cod fish]] ({{w|Gadidae}}), today it is a {{w|dietary supplement}}. ||
 
|-
 
| 1822 || {{w|Rickets}} || || Sniadecki observes that lack of sunlight exposure is likely a cause of rickets.<ref name="Holimicf"/>
 
|-
 
| 1824 || || || Although having been used medicinally for a long time, {{w|cod liver oil}} (which has vitamin D) is first prescribed by D. Scheutte for the treatment of rickets.<ref name="Wolfv"/> ||
 
|-
 
| 1849 || {{w|Rickets}} || || "In 1849, Williams reported the results of administering fish liver oil (vitamin D) to 234 patients with TB (5). He noted that even in a few days…the appetite, flesh and strength were gradually improved“ and concluded that ”the pure fresh oil from the liver of the cod is more beneficial in the treatment of pulmonary consumption than any agent, medicinal, dietetic, or regiminal, that has yet been employed“. Tiny Tim did not die prematurely despite fish liver oil not being included in his diet."<ref name="Evolutionary Pe">{{cite journal |last1=Hochberg |first1=Ze'ev |last2=Hochberg |first2=Irit |title=Evolutionary Perspective in Rickets and Vitamin D |journal=Frontiers in Endocrinology |date=15 May 2019 |volume=10 |doi=10.3389/fendo.2019.00306 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529528/ |issn=1664-2392}}</ref>
 
|-
 
| 1849 || || || {{w|Cod liver oil}} is recognized in Europe as beneficial in the treatment of {{w|tuberculosis}}.<ref name="Holimicf"/> || {{w|Europe}}
 
|-
 
| 1890 || {{w|Rickets}} || || British medical missionary and epidemiologist Theodore Palm notes through his travels that children living in equatorial countries do not develop {{w|rickets}}.<ref name="Mohrv"/> ||
 
|-
 
| 1903 || || || Faroese physician {{w|Niels Ryberg Finsen}} is awarded the Nobel Prize in Physiology or Medicine for his discovery that shortwave ultraviolet light is effective in the treatment of cutaneous tuberculosis.<ref name="Litonjua"/>
 
|-
 
| 1906 || {{w|Rickets}} || || English biochemist {{w|Frederick Gowland Hopkins}} postulates the existence of essential dietary factors necessary for the prevention of diseases such as {{w|scurvy}} or {{w|rickets}}.<ref name="Wolfv"/> ||
 
|-
 
| 1912 || || Scientific development || Hopkins describes the vitamins.<ref name="Hochberg"/>
 
|-
 
| 1914 || {{w|Rickets}} || || McCollum and co-workers conduct a series of experiments that would lead to the discovery of vitamin D. The team manages to isolate a substance from butterfat, necessary for prevention of {{w|xerophthalmia}} in rats, and name it “fat-soluble factor A”. They subsequently report that heated oxidized cod-liver oil could not prevent xerophthalmia but could cure rickets in rats, and conclude that “fatsoluble factor A” consists of two entities, one which could prevent xerophthalmia (subsequently called vitamin A) and one which cured rickets (subsequently called vitamin D, as the terms vitamin B and vitamin C have already been coined).<ref name="Litonjua"/> ||
 
|-
 
| 1919 || || || British biochemist {{w|Edward Mellanby}} observes that dogs who were fed a diet of mostly oatmeal and kept indoors away from the sun could be cured of the disease by providing cod liver oil.<ref name="What's Up, USANA?">{{cite web |title=The History and Discovery of Vitamins Through The Ages |url=https://whatsupusana.com/2017/04/vitamin-discovery/ |website=What's Up, USANA? |access-date=14 September 2021 |date=27 April 2017}}</ref> || {{w|United Kingdom}}
 
|-
 
| 1921 || {{w|Rickets}} || || Hess and Unger observe that “seasonal incidence of rickets is due to seasonal variations of sunlight.”<ref name="Wolfv"/> ||
 
|-
 
| 1922 || {{w|Rickets}} || || Elmer McCollum at Johns Hopkins University discovers Vitamin D from cod liver oil as a dietary substance that could prevent rickets.<ref name="Wageningen"/> ||
 
|-
 
| 1922 || {{w|Rickets}} || || Sniadecki notices that children living on farms in Poland do not develop rickets, in contrast to children living in the city of {{w|Warsaw}}, who has high incidence of the disease at the time. He hypothesizes that increased exposure to sunlight in the children living in rural areas prevents them from developing rickets.<ref name="Mohrv">{{cite journal |last1=Mohr |first1=Sharif B. |title=A Brief History of Vitamin D and Cancer Prevention |journal=Annals of Epidemiology |date=February 2009 |volume=19 |issue=2 |pages=79–83 |doi=10.1016/j.annepidem.2008.10.003}}</ref> || {{w|Poland}}
 
|-
 
| 1922 || {{w|Rickets}} || || "A landmark investigation was that of Hariette Chick and her co-workers (6) who, in 1922, working with malnourished children in a clinic in post-World War I Vienna, showed that rickets prevalent in the children could be cured by whole milk or cod-liver oil."<ref name="Wolfv"/> ||
 
|-
 
| 1923 || || Scientific development || Goldblatt and Soames show the conversion of a precursor to vitamin D in the skin under the effect of ultraviolet light.<ref name="Hochberg"/>
 
 
|-
 
|-
| 1925 || || || “The  process of irradiation, of either the patient or the food consumed by the patient led to  antirachitic protection - a discovery that was patented in 1925 by the University of  Wisconsin. It is now clear that some materials, such as cod liver oil, contain vitamin D  and many other foods contain a provitamin, which is converted upon irradiation to  vitamin D.” <ref name="milnde">{{cite book |last1=Milne |first1=G. W. A. |last2=Delander |first2=M. |title=Vitamin D Handbook: Structures, Synonyms, and Properties |date=2008 |publisher=John Wiley & Sons |isbn=978-0-470-13983-7 |url=https://books.google.com.ar/books?id=RG4yX1Y1IdwC&printsec=frontcover&dq=Vitamin+D+Handbook&hl=en&sa=X&redir_esc=y#v=onepage&q=Vitamin%20D%20Handbook&f=false |access-date=31 August 2021 |language=en}}</ref>
+
| 1650 || {{w|Rickets}} || Prelude || {{w|Rickets}} is described in detail by British physician {{w|Francis Glisson}}.<ref name="Wolfv">{{cite journal |last1=Wolf |first1=George |title=The Discovery of Vitamin D: The Contribution of Adolf Windaus |journal=The Journal of Nutrition |date=1 October 2004 |volume=134 |issue=6 |pages=1299–1302 |doi=10.1093/jn/134.6.1299}}</ref> || {{w|United Kingdom}}
 
|-
 
|-
| 1926 || || || "Rosenheim and Webster, at a meeting of the Biochemical Society in London in 1926 (22) announced that “the precursor of vitamin D is not cholesterol itself, but a substance which is associated with and follows ‘chemically pure' cholesterol in all its stages of purification by the usual methods (saponification and recrystallization).” "<ref name="Wolfv"/> ||
+
| 1770 || {{w|Tuberculosis}} || Prelude (medical development) || {{w|Cod liver oil}}, rich in {{w|vitamin D}}, is first advocated for the treatment of {{w|tuberculosis}}.<ref>{{cite web |title=Cod Liver Oil - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cod-liver-oil |website=www.sciencedirect.com |access-date=11 August 2021}}</ref> Derived from [[w:liver (food)|liver]] of [[w:cod|cod fish]] ({{w|Gadidae}}), today it is a {{w|dietary supplement}}. ||  
 
|-
 
|-
| 1928 || {{w|Tooth decay}} || || An experiment by Mellanby and Pattison with children finds that oral vitamin D intake reduces the risk of dental caries.<ref name="Wageningen"/>
+
| 1822 || {{w|Rickets}} || Prelude (research) || Polish physician {{w|Jędrzej Śniadecki}} observes that lack of sunlight exposure is likely a cause of rickets.<ref>W. Mozolowski: Jedrzej Sniadecki (1768–1883) on the cure of rickets. Nature 143:121 (1939)</ref> || {{w|Poland}}
 
|-
 
|-
| 1930 || || || “vitamin D2 has been used as a dietary supplement in lieu of vitamin D3 since the 1930s” <ref name="Holimicf"/>
+
| 1824 || {{w|Rickets}} || Prelude (medical development) || Although having been used medicinally for a long time, {{w|cod liver oil}} (which has vitamin D) is first prescribed by D. Scheutte for the treatment of rickets.<ref name="Wolfv"/> ||
 
|-
 
|-
| 1930 || || || “This example of a vitamin D prodrug represents the oldest vitamin D analog and was developed in the 1930s as a method of stabilizing the triene structure of one of the photoisomers of vitamin D” <ref name="Holimicf"/>
+
| 1849 || {{w|Tuberculosis}} || Prelude (research) || English physician {{w|Charles Theodore Williams}} reports the results of administering fish liver oil (vitamin D) to 234 patients with {{w|tuberculosis}}. He notes an important improvement in a few days and concludes that ”the pure fresh oil from the liver of the cod is more beneficial in the treatment of pulmonary consumption than any agent, medicinal, dietetic, or regiminal, that has yet been employed“.<ref name="Evolutionary Pe">{{cite journal |last1=Hochberg |first1=Ze'ev |last2=Hochberg |first2=Irit |title=Evolutionary Perspective in Rickets and Vitamin D |journal=Frontiers in Endocrinology |date=15 May 2019 |volume=10 |doi=10.3389/fendo.2019.00306 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529528/ |issn=1664-2392}}</ref> || {{w|United Kingdom}}
 
|-
 
|-
| 1931 || || Scientific development || Vitamin D<sub>2</sub> is purified and crystallized simultaneously by researchers in {{w|London}} and the {{w|Netherlands}}.<ref name="Litonjua"/><ref name="Wolfv"/> || {{w|United Kingdom}}, {{w|Netherlands}}
+
| 1849 || {{w|Tuberculosis}} || Prelude (medical development) || {{w|Cod liver oil}} is recognized in Europe as beneficial in the treatment of {{w|tuberculosis}}.<ref name="Holimicf"/> || {{w|Europe}}
 
|-
 
|-
| 1932 || || || "Since the idea of Vitamin D had become clear, its vitamin structure was identified in 1932 when Askew et al. were able to isolate vitamin D2  from a mixture of ergosterol (a compound found in fungi)"<ref name="What's Up, USANA?"/> ||
+
| 1890 || {{w|Rickets}} || Prelude (research) || British medical missionary and epidemiologist Theodore Palm notes through his travels that children living in equatorial countries do not develop {{w|rickets}}.<ref name="Mohrv"/> ||
 
|-
 
|-
| 1936 || || || {{w|Cholecalciferol}} is first described.<ref>{{cite book |last1=Fischer |first1=János |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |url=https://books.google.com.ar/books?id=FjKfqkaKkAAC&pg=PA451&redir_esc=y#v=onepage&q&f=false |language=en}}</ref>
+
| 1903 || {{w|Tuberculosis}} || Prelude (research) || Faroese physician {{w|Niels Ryberg Finsen}} is awarded the Nobel Prize in Physiology or Medicine for his discovery that shortwave ultraviolet light is effective in the treatment of cutaneous tuberculosis.<ref name="Litonjua"/> ||
 
|-
 
|-
| 1936 || || || “A great deal of chemical work ensued, mainly in Germany, the UK and the US  and led in 1936 to the assignment of structure to vitamin D, as a C28 steroid, an  ergosterol derivative with ring B opened (Record Number 531). Within a year, a second  antirachitic compound, formed by irradiation of non-ergosterol steroids was isolated and  characterized as a C27 steroid and named vitamin D” <ref name="milnde"/>
+
| 1906 || {{w|Rickets}} || Prelude (research) || English biochemist {{w|Frederick Gowland Hopkins}} postulates the existence of essential dietary factors necessary for the prevention of diseases such as {{w|scurvy}} or {{w|rickets}}.<ref name="Wolfv"/><ref>{{cite web |last1=Hopkins |first1=F. Gowland |title=The analyst and the medical man |url=https://pubs.rsc.org/en/content/articlelanding/1906/an/an906310385b/unauth |website=Analyst |access-date=22 September 2021 |pages=385b–404 |language=en |doi=10.1039/AN906310385B |date=1 January 1906}}</ref> || {{w|United Kingdom}}
 
|-
 
|-
| 1936 || {{w|Skin cancer}} || || S. Peller observes that U.S. Navy personnel who experiences skin cancer has a much lower incidence of nonskin cancers. This leads him to hypothesize that the development of skin cancer confers protection against other cancers. This marks the beginning of the emergence of the epidemiologic role of sunlight in cancer prevention.<ref name="Mohrv"/> || {{w|United States}}  
+
| 1912 || || Prelude (research) || {{w|Frederick Gowland Hopkins}} describes the {{w|vitamin}}s.<ref name="Hochberg"/> || {{w|United Kingdom}}
 
|-
 
|-
| 1937 || {{w|Rickets}} || || The term "rickets resistant to vitamin D" is coined by Albright et al., as the patients they describe present with changes in mineral metabolism that could only be overcome by very large daily doses of vitamin D.<ref name="Hochberg">{{cite book |last1=Hochberg |first1=Z. |title=Vitamin D and Rickets |date=2003 |publisher=Karger |isbn=978-3-8055-7582-9 |url=https://books.google.com.ar/books/about/Vitamin_D_and_Rickets.html?id=OdBsAAAAMAAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
+
| 1914 || {{w|Rickets}} || Prelude (research) || McCollum and co-workers conduct a series of experiments that would lead to the discovery of vitamin D. The team manages to isolate a substance from butterfat, necessary for prevention of {{w|xerophthalmia}} in rats, and name it “fat-soluble factor A”. They subsequently report that heated oxidized cod-liver oil could not prevent xerophthalmia but could cure rickets in rats, and conclude that “fatsoluble factor A” consists of two entities, one which could prevent xerophthalmia (subsequently called vitamin A) and one which cured rickets (subsequently called vitamin D, as the terms vitamin B and vitamin C have already been coined).<ref name="Litonjua"/><ref>{{cite journal |last1=McCollum |first1=E.V. |last2=Davis |first2=Marguerite |title=OBSERVATIONS ON THE ISOLATION OF THE SUBSTANCE IN BUTTER FAT WHICH EXERTS A STIMULATING INFLUENCE ON GROWTH |journal=Journal of Biological Chemistry |date=October 1914 |volume=19 |issue=2 |pages=245–250 |doi=10.1016/S0021-9258(18)88306-5}}</ref> || {{w|United States}} ({{w|Wisconsin Agricultural Experiment Station}}, {{w|University of Wisconsin–Madison}})
 
|-
 
|-
| 1937 || || || German chemist {{w|Adolf Windaus}} and colleagues discover 7-dehydrocholesterol (7- DHC), the precursor of vitamin D<sub>3</sub>, by isolating 7-DHC from animal skin and inducing formation of vitamin D<sub>3</sub> by irradiating 7-DHC with {{w|ultraviolet}} radiation. Windaus would receive the {{w|Nobel Prize in Chemistry}} in 1939 for this work, which unifies two apparently disparate lines of evidence through the discovery that exposure to UV is responsible for vitamin D synthesis.<ref name="Mohrv"/> || {{w|Germany}}
+
| 1919 || || Prelude (research) || British biochemist {{w|Edward Mellanby}} observes that dogs who were fed a diet of mostly oatmeal and kept indoors away from the sun could be cured of the disease by providing cod liver oil.<ref name="What's Up, USANA?">{{cite web |title=The History and Discovery of Vitamins Through The Ages |url=https://whatsupusana.com/2017/04/vitamin-discovery/ |website=What's Up, USANA? |access-date=14 September 2021 |date=27 April 2017}}</ref> || {{w|United Kingdom}}
 
|-
 
|-
| 1937 || || || The isolation and identification of the vitamin D nutritional compounds are completed, drawing to a close an important era of vitamin D investigation.<ref name="DeLuca">{{cite book |last1=DeLuca |first1=H. F. |title=Vitamin D: Metabolism and Function |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-81306-1 |url=https://books.google.com.ar/books/about/Vitamin_D.html?id=-xArBAAAQBAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||  
+
| 1921 || {{w|Rickets}} || Prelude (research) || Hess and Unger observe that “seasonal incidence of rickets is due to seasonal variations of sunlight.<ref name="Wolfv"/> ||
 
|-
 
|-
| 1930s || {{w|Rickets}} || || “The essential role of vitamin D in mineral homeostasis and skeletal health has been recognized since the 1930s, when vitamin D fortification of milk eradicated rickets” <ref name="Holimicf"/> ||
+
| 1922 || {{w|Rickets}} || Research || American biochemist {{w|Elmer McCollum}} at {{w|Johns Hopkins University}} discovers Vitamin D from cod liver oil as a dietary substance that could prevent rickets.<ref name="Wageningen"/> || {{w|United States}}
 
|-
 
|-
| 1930 || {{w|Rickets}} || || “This was the major source of vitamin D used to fortify milk and to treat rickets spearheading the public health campaign that successfully eradicated rickets in North America by the 1930s, only to see it surface again with the new century” <ref name="Holimicf"/> ||
+
| 1922 || {{w|Rickets}} || Research || Sniadecki notices that children living on farms in Poland do not develop rickets, in contrast to children living in the city of {{w|Warsaw}}, who has high incidence of the disease at the time. He hypothesizes that increased exposure to sunlight in the children living in rural areas prevents them from developing rickets.<ref name="Mohrv">{{cite journal |last1=Mohr |first1=Sharif B. |title=A Brief History of Vitamin D and Cancer Prevention |journal=Annals of Epidemiology |date=February 2009 |volume=19 |issue=2 |pages=79–83 |doi=10.1016/j.annepidem.2008.10.003}}</ref> || {{w|Poland}}
 
|-
 
|-
| Early 1940s || || || “The effects vitamin D might exert in rheumatoid arthritis disease pathogenesis were recognized in the early 1940s when it was noticed that patients with rheumatoid arthritis were prone to an increased susceptibility to bone fractures” <ref name="Holimicf"/> ||
+
| 1922 || {{w|Rickets}} || Research || British microbiologist {{w|Hariette Chick}} and her co-workers, working with malnourished children in a clinic in {{w|Vienna}}, show that rickets prevalent in the children could be cured by whole milk or cod-liver oil.<ref name="Wolfv"/> || {{w|Austria}}
 
|-
 
|-
| 1940 || || || “Since the early 1940s, the United States and Canada have set dietary intake recommendations for nutrients. The first recommendation for vitamin D for Americans in 1941 gave the value of 400 IU (i.e., the lower value of a range for infants at the time), for adults in a footnote only, that stated “When not available from sunshine, [vitamin D] should be provided up to the minimal amounts recommended for infants”” <ref name="Holimicf"/>
+
| 1923 || {{w|Rickets}} || Research || Harry Goldblatt and Katharine Marjorie Soames show the conversion of a precursor to vitamin D in the skin under the effect of ultraviolet light. They also observe that livers of irradiated rats are curative when fed to rachitic rats.<ref>{{cite journal |last1=Goldblatt |first1=Harry |last2=Soames |first2=Katharine Marjorie |title=Studies on the Fat-Soluble Growth-Promoting Factor: (I) Storage. (II) Synthesis |journal=Biochemical Journal |date=1 January 1923 |volume=17 |issue=4-5 |pages=446–453 |doi=10.1042/bj0170446}}</ref><ref name="Hochberg"/> ||
 
|-
 
|-
| 1942 || Internal cancers || || Apperly first observes that there are lower overall mortality rates from internal cancers in sunnier regions of the United States.<ref name="Mohrv"/> || {{w|United States}}
+
| 1926 || || Research || Rosenheim and Webster, at a meeting of the Biochemical Society in London, announce that “the precursor of vitamin D is not cholesterol itself, but a substance which is associated with and follows ‘chemically pure' cholesterol in all its stages of purification by the usual methods (saponification and recrystallization).<ref name="Wolfv"/> || {{w|United Kingdom}}
 
|-
 
|-
| 1946 || || || Dowling et al. report the treatment of patients with {{w|lupus vulgaris}} with oral vitamin D. Eighteen of 32 patients appear to be cured, with nine improved.<ref name="Litonjua">{{cite book |last1=Litonjua |first1=Augusto A. |title=Vitamin D and the Lung: Mechanisms and Disease Associations |date=23 May 2012 |publisher=Springer Science & Business Media |isbn=978-1-61779-888-7 |url=https://books.google.com.ar/books?id=JKUA6_7kcuwC&printsec=frontcover&dq=Vitamin+D+and+the+Lung&hl=en&sa=X&redir_esc=y#v=onepage&q=Vitamin%20D%20and%20the%20Lung&f=false |language=en}}</ref>
+
| 1928 || {{w|Tooth decay}} || Research || An experiment by Mellanby and Pattison with children finds that oral vitamin D intake reduces the risk of dental caries.<ref name="Wageningen"/> ||
 
|-
 
|-
| 1950 || || ||“In Europe, most countries do not fortify milk with vitamin D because in the 1950s there was an outbreak of vitamin D intoxication in young children resulting in laws that forbade the fortification of foods with vitamin D (4)”<ref name="Holimicf"/>
+
| 1930 || || Drug launch || Vitamin D prodrug {{w|dihydrotachysterol}} is developed as a method of stabilizing the triene structure of one of the photoisomers of vitamin D. This represents the oldest vitamin D analog.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1952 || || || Synthetic vitamin D2 and D3 compounds start being produced.<ref name="Torres"/>
+
| 1931 || || Research || Vitamin D<sub>2</sub> is purified and crystallized simultaneously by researchers in {{w|London}} and the {{w|Netherlands}}.<ref name="Litonjua"/><ref name="Wolfv"/> || {{w|United Kingdom}}, {{w|Netherlands}}
 
|-
 
|-
| 1955 || || || The complete photochemical and thermal reaction steps from {{w|ergosterol}} to {{w|calciferol}} are elucidated by Velluz et al.<ref name="Wolfv"/> || {{w|France}}
+
| 1932 || || Research || The structure of vitamin D is identified when Askew et al. manage to isolate vitamin D<sub>2</sub> from a mixture of {{w|ergosterol}} (a compound found in {{w|fungi}}).<ref name="What's Up, USANA?"/> ||
 
|-
 
|-
| 1957 || || || “In the United States, the American Medical Association’s Council on Foods and Nutrition recommended in 1957 that milk should contain 400 IU (10 μg) per quart and that the vitamin D content be measured at least twice yearly by an independent laboratory” <ref name="Holimicf"/>
+
| 1933 || || Research || Holtz develops {{w|dihydrotachysterol}},<ref name="">{{cite book |last1=McCann |first1=S. M. |title=Endocrinology: People and Ideas |date=27 May 2013 |publisher=Springer |isbn=978-1-4614-7436-4 |url=https://books.google.com.ar/books?id=0cXkBwAAQBAJ&pg=PA262&lpg=PA262&dq=dihydrotachysterol+%22in+1930..1939%22&source=bl&ots=aLRUb8VA02&sig=ACfU3U0QwKXfkA2e1vQMTnB5uX0BptsVVg&hl=en&sa=X&ved=2ahUKEwjP7u-12pDzAhVPrZUCHVryB6sQ6AF6BAgDEAM#v=onepage&q=dihydrotachysterol%20%22in%201930..1939%22&f=false |language=en}}</ref> a synthetic analog of vitamin D that does not require renal activation like vitamin D<sub>2</sub> or vitamin D<sub>3</sub>.<ref>{{cite web |title=Dihydrotachysterol |url=https://go.drugbank.com/drugs/DB01070 |website=go.drugbank.com |access-date=21 September 2021}}</ref> || 
 
|-
 
|-
| 1958 || || || “In the 1958 British Birth Cohort study, 25(OH)D was inversely associated with prevalent elevated hemoglobin A1c (74). In the Rancho Bernardo study, a community-based cohort of older adults in southern California, 25(OH)D was inversely associated with prevalent hyperglycemia only among men” <ref name="Holimicf"/>
+
| 1936 || || Research || {{w|Cholecalciferol}} is first described.<ref>{{cite book |last1=Fischer |first1=János |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |url=https://books.google.com.ar/books?id=FjKfqkaKkAAC&pg=PA451&redir_esc=y#v=onepage&q&f=false |language=en}}</ref>  Also known as vitamin D<sub>3</sub>, it is a type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a {{w|dietary supplement}}.<ref>{{cite book |title=Nutrition in the prevention and treatment of disease |date=2013 |publisher=Boston |location=Amsterdam |isbn=9780123918840 |edition=3rd}}</ref> ||
 
|-
 
|-
| 1950s || || || “In the 1950s, there was an outbreak of presumed vitamin D intoxication in infants and young children” <ref name="Holimicf"/>
+
| 1936 || {{w|Skin cancer}} || Research || S. Peller observes that U.S. Navy personnel who experiences skin cancer has a much lower incidence of nonskin cancers. This leads him to hypothesize that the development of skin cancer confers protection against other cancers. This marks the beginning of the emergence of the epidemiologic role of sunlight in cancer prevention.<ref name="Mohrv"/> || {{w|United States}}
 
|-
 
|-
| 1950s || || || “In the 1950s, there was an outbreak of neonatal hypercalcemia. In Great Britain that was thought to be due to over-fortification of milk of vitamin D” <ref name="Holimicf"/>
+
| 1937 || {{w|Rickets}} || Research || The term "rickets resistant to vitamin D" is coined by Albright et al., as the patients they describe present with changes in mineral metabolism that could only be overcome by very large daily doses of vitamin D.<ref name="Hochberg">{{cite book |last1=Hochberg |first1=Z. |title=Vitamin D and Rickets |date=2003 |publisher=Karger |isbn=978-3-8055-7582-9 |url=https://books.google.com.ar/books/about/Vitamin_D_and_Rickets.html?id=OdBsAAAAMAAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1960 || || || (OH)2D3 was the first dihydroxylated metabolite to be identified back in the late 1960s (50) and yet it is still the most poorly understood” <ref name="Holimicf"/>
+
| 1937 || || Research || German chemist {{w|Adolf Windaus}} and colleagues discover {{w|7-Dehydrocholesterol}} (7- DHC), the precursor of vitamin D<sub>3</sub>, by isolating 7-DHC from animal skin and inducing formation of vitamin D<sub>3</sub> by irradiating 7-DHC with {{w|ultraviolet}} radiation. Windaus would receive the {{w|Nobel Prize in Chemistry}} in 1939 for this work, which unifies two apparently disparate lines of evidence through the discovery that exposure to UV is responsible for vitamin D synthesis.<ref name="Mohrv"/> || {{w|Germany}}
 
|-
 
|-
| 1960 || || || “In the 1960s, vitamin D was considered the cause of supravalvular stenosis (52, 56, 73, 74). The published hypothesis was that “toxic” amounts of vitamin D during pregnancy gave rise to a clinical condition titled “infantile hypercalcemia syndrome”” <ref name="Holimicf"/>
+
| 1937 || || Research || The isolation and identification of the vitamin D nutritional compounds are completed, drawing to a close an important era of vitamin D investigation.<ref name="DeLuca">{{cite book |last1=DeLuca |first1=H. F. |title=Vitamin D: Metabolism and Function |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-81306-1 |url=https://books.google.com.ar/books/about/Vitamin_D.html?id=-xArBAAAQBAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1960 || {{w|Skin cancer}} || || “Large sun-safety campaigns have been initiated, which seem to have had a significant impact, since the increasing trend of skin cancer incidence rates observed from 1960 is reversed for young persons after about 1990 (5). However, in the same time period, i.e. after 1990, vitamin D deficiency became prevalent in many populations” <ref name="Holimicf"/>
+
| 1940 || || Recommendation || The first recommendation for vitamin D is established in the United States, determining the value of 400 IU (i.e., the lower value of a range for infants at the time), for adults in a footnote only, that states “When not available from sunshine, [vitamin D] should be provided up to the minimal amounts recommended for infants”.<ref name="Holimicf"/> || {{w|United States}}
 
|-
 
|-
| 1960 || {{w|Skin cancer}} || || “Large sun-safety campaigns have been initiated, which seem to have had a significant impact, since the increasing trend of skin cancer incidence rates observed from 1960 is reversed for young persons after about 1990 (5). However, in the same time period, i.e. after 1990, vitamin D deficiency became prevalent in many populations (3). Since solar UV is a main source of vitamin D, this deficiency may, at least partly, be due to reduced sun exposure.” <ref name="Holimicf"/>
+
| 1942 || {{w|Cancer}} (internal) || Research || Apperly first observes that there are lower overall mortality rates from internal cancers in sunnier regions of the United States.<ref name="Mohrv"/> || {{w|United States}}
 
|-
 
|-
| 1963 || {{w|Rickets}} || || “Teotia et al. carried out several epidemiological surveys during 1963–2005 and reported 17,286 cases of rickets, 11,900 of infantile rickets due to lack of sunlight exposure, and 3 with congenital rickets born to mothers with vitamin D osteomalacia” <ref name="Holimicf"/>
+
| 1946 || {{w|Lupus vulgaris}} || Research || Dowling et al. report the treatment of patients with {{w|lupus vulgaris}} with oral vitamin D. Eighteen of 32 patients appear to be cured, with nine improved.<ref name="Litonjua">{{cite book |last1=Litonjua |first1=Augusto A. |title=Vitamin D and the Lung: Mechanisms and Disease Associations |date=23 May 2012 |publisher=Springer Science & Business Media |isbn=978-1-61779-888-7 |url=https://books.google.com.ar/books?id=JKUA6_7kcuwC&printsec=frontcover&dq=Vitamin+D+and+the+Lung&hl=en&sa=X&redir_esc=y#v=onepage&q=Vitamin%20D%20and%20the%20Lung&f=false |language=en}}</ref>
 
|-
 
|-
| 1963 || || || “Reports by the American Academy of Pediatrics were more cautious in linking vitamin D with these diseases in 1963 (6) and in 1967 concluded the hypothesis that vitamin D caused infantile hypercalcemia was unproven” <ref name="Holimicf"/>
+
| 1952 || || Product launch || Synthetic vitamin D<sub>2</sub> and D<sub>3</sub> compounds start being produced.<ref name="Torres"/> ||
 
|-
 
|-
| 1963 || || || The {{w|American Academy of Pediatrics}} (AAP) Committee on Nutrition recommends a dose of vitamin D of 10 micrograms (400 IU) daily as the standard of care for children.<ref name="Frank R">{{cite web |last1=Greer |first1=Frank R |title=Issues in establishing vitamin D recommendations for infants and children |url=https://watermark.silverchair.com/1759s.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAscwggLDBgkqhkiG9w0BBwagggK0MIICsAIBADCCAqkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMEwfbhIogqJ7sc9DMAgEQgIICeihmZk4yEbSzy0AgIB2Mj6zXVdk6RQ23UM8sPS30j7bEmC8LCap-beKafairFUkV8DaTFbLX6YMxylxgIRi4f2Y6duWI_e0e6ZiwjzRcGyynhVlDgv647GSZvXIsau9sLBSruCeZwNdfWZa7NPHVY81PV--6hUyebIFhUxbg3G5DdXB_XWTvvD-SiJpj53-rTX7CGE7ZqLlL9WB8bCaKV3XdarKYNgNXr0S3OTX-fvwDuzo95z1BHa8kWLTxBhInFUIDUaaZM5aO2cTPsh00hvVBFxK6SSGW198Jw70NtiPko_19Voyx4iabh2AgkGi58qkabJO-2R84411TxxnVgWx2Lm6j4hqlp_ij8gceYKo1KVJfWzyT-pV2csGU54zARC-sKkuPhPrFO49eABsjm-2eguzyUa7Al94S4J01RUxeZkfsdOnLoC5HgqfEPsbDaJaX7blA4D8kP-zD7bPRoC4jQEvmFXnwgUAaMj9TfvKieZfgyitZNoFcVzMV--rcVhCnbbULo3IjrsxnJh4jiWa9VesCi8DPaHO8PIHEloOf2fk7b4BDWnz5czo03O0cdtCEz-7r74VHFBmu3HBcTbSOB_tXSGSddNF6W2Uud2k_-SZroaiM2EuvLT94L6oJLFYRvzUapzjMnJif2UAdqWsCpSsM___76QSBXEszWQ27g5oR405IcyOXAMvgdVDdyTMD5CfMx2Ivf93Iui1oIGfpdO5pSPE9aPm8ifm32wnsxIl1rgwrv2QsIM98t5D7CaBiLylsAOCLwhHDNPU80k0zfo5JZH82VSc_NHr_pqYVqIgAFZazNCZXbTr3bxf0aYUC6KO6POQeZcA |website=watermark.silverchair.com}}</ref>
+
| 1953–1955 || || Notable case || Nutrition surveys indicate that the normal British infant could ingest from various sources as much as 4,000 IU of vitamin D per day. This is coincident with numerous cases of infantile hypercalcemia mainly of the mild form. In the following years the food enrichment policies would change and subsequently make the incidence of infantile hypercalcemia fall.<ref name="sdfsd">{{cite web |last1=Paunier |first1=Luc |title=Prevention of Rickets |url=https://www.nestlenutrition-institute.org/sites/default/files/documents-library/publications/secured/5ed6568a397fd230d00c5900431ce8d2.pdf |website=nestlenutrition-institute.org |access-date=}}</ref> || {{w|United Kingdom}}
 
|-
 
|-
| 1963 || || Recommendation || “The US Food and Drug Administration’s (FDA) Daily Recommended Allowance of vitamin D is 400 IU (44), consistent with the recommendations of the 1963 American Academy of Pediatrics (AAP) Committee on Nutrition” <ref name="Holimicf"/>
+
| 1955 || || Research || The complete photochemical and thermal reaction steps from {{w|ergosterol}} to {{w|calciferol}} are elucidated by Velluz et al.<ref name="Wolfv"/> || {{w|France}}
 
|-
 
|-
| 1963 || || Recommendation || The American Academy of Pediatrics Committee on Nutrition recommends that all infants receive 10μg (400 IU) of vitamin D per day.<ref name="Hochberg"/>
+
| 1957 || || Recommendation || The American Medical Association’s Council on Foods and Nutrition recommends that milk should contain 400 IU (10 μg) per quart and that the vitamin D content be measured at least twice yearly by an independent laboratory.<ref name="Holimicf"/> || {{w|United States}}
 
|-
 
|-
| 1965–1975 || || || In this period, the elements of the vitamin D endocrine system that regulate calcium and phosphorus become clear.<ref>{{cite journal |last1=DeLuca |first1=Hector F |title=History of the discovery of vitamin D and its active metabolites |journal=BoneKEy Reports |date=8 January 2014 |volume=3 |doi=10.1038/bonekey.2013.213}}</ref> ||
+
| 1958 || {{w|Diabetes}} || Research || In a [[w:British birth cohort studies|British birth cohort study]], {{w|calcifediol}} is inversely associated with prevalent elevated {{w|hemoglobin A1c}}.<ref>{{cite journal |last1=Hypponen |first1=E. |last2=Boucher |first2=B. J. |last3=Berry |first3=D. J. |last4=Power |first4=C. |title=25-Hydroxyvitamin D, IGF-1, and Metabolic Syndrome at 45 Years of Age: A Cross-Sectional Study in the 1958 British Birth Cohort |journal=Diabetes |date=1 February 2008 |volume=57 |issue=2 |pages=298–305 |doi=10.2337/db07-1122}}</ref> || {{w|United Kingdom}} (Institute of Child Health, {{w|London}})
 
|-
 
|-
| 1966 || || Scientific development || Wasserman and his colleagues discover the existence of a calcium-binding protein in the intestines of chicks given vitamin D.<ref name="DeLuca"/> ||
+
| 1960s || {{w|Skin cancer}} || Notable case ||  An increasing trend of skin cancer incidence rates starts being observed from this time, leading to large sun-safety campaigns.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1967 || || Scientific development || Loomis suggests that melanin pigmentation evolved for protection from vitamin intoxication because of excessive exposure to sunlight.<ref name="Holimicf"/>
+
| 1960 || || Research || 25,26-Dihydroxyvitamin D3(25,26-dihydroxycholecalciferol) becomes the first dihydroxylated metabolite to be identified.<ref>{{cite journal |last1=DeLuca |first1=Hector F. |last2=Suda |first2=Tatsuo |last3=Schnoes |first3=Heinrich K. |last4=Tanaka |first4=Yoko |last5=Holick |first5=Michael F. |title=25,26-Dihydroxycholecalciferol, a metabolite of vitamin D3 with intestinal calcium transport activity |journal=Biochemistry |date=1 November 1970 |volume=9 |issue=24 |pages=4776–4780 |doi=10.1021/bi00826a022}}</ref> It is a metabolite of vitamin D3 with intestinal calcium transport activity.<ref>{{cite web |title=25,26-Dihydroxyvitamin D3 (25,26-Dihydroxycholecalciferol) {{!}} VD/VDR Activator {{!}} MedChemExpress |url=https://www.medchemexpress.com/25,26-dihydroxyvitamin-d3.html |website=MedchemExpress.com |access-date=21 September 2021}}</ref> ||
 
|-
 
|-
| 1968 || || || “In the context of vitamin D safety, the reference to 2,000 IU/day has remained unchanged since the number was first mentioned in the 1968 Recommended Dietary Allowance book where the dose was implicated in infantile hypercalcemia” <ref name="Holimicf"/> “In the context of vitamin D safety, the reference to 2,000 IU/day has remained unchanged since the number was first mentioned in the 1968 Recommended Dietary Allowance book where the dose was implicated in infantile hypercalcemia” <ref name="Holimicf"/>
+
| 1960s || {{w|Supravalvular stenosis}} || Research || During this time, vitamin D is considered the cause of {{w|supravalvular stenosis}}.<ref name="Holimicf"/> The published hypothesis is that “toxic” amounts of vitamin D during pregnancy gave rise to a clinical condition titled “infantile hypercalcemia syndrome”.<ref>{{cite journal |last1=Friedman |first1=William F. |title=Vitamin D as a cause of the supravalvular aortic stenosis syndrome |journal=American Heart Journal |date=May 1967 |volume=73 |issue=5 |pages=718–720 |doi=10.1016/0002-8703(67)90186-x}}</ref> ||
 
|-
 
|-
| 1968 || || Scientific development || Team led by {{w|Hector DeLuca}} at the {{w|University of Wisconsin}} isolate an active substance identified as 25-hydroxyvitamin D3, which the team later proves to be produced in the {{w|liver}}.<ref name="Hochberg"/> || {{w|United States}}
+
| 1963 || || Recommendation || The {{w|American Academy of Pediatrics}} (AAP) Committee on Nutrition recommends a dose of vitamin D of 10 micrograms (400 IU) daily as the standard of care for children.<ref name="Frank R">{{cite web |last1=Greer |first1=Frank R |title=Issues in establishing vitamin D recommendations for infants and children |url=https://watermark.silverchair.com/1759s.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAscwggLDBgkqhkiG9w0BBwagggK0MIICsAIBADCCAqkGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMEwfbhIogqJ7sc9DMAgEQgIICeihmZk4yEbSzy0AgIB2Mj6zXVdk6RQ23UM8sPS30j7bEmC8LCap-beKafairFUkV8DaTFbLX6YMxylxgIRi4f2Y6duWI_e0e6ZiwjzRcGyynhVlDgv647GSZvXIsau9sLBSruCeZwNdfWZa7NPHVY81PV--6hUyebIFhUxbg3G5DdXB_XWTvvD-SiJpj53-rTX7CGE7ZqLlL9WB8bCaKV3XdarKYNgNXr0S3OTX-fvwDuzo95z1BHa8kWLTxBhInFUIDUaaZM5aO2cTPsh00hvVBFxK6SSGW198Jw70NtiPko_19Voyx4iabh2AgkGi58qkabJO-2R84411TxxnVgWx2Lm6j4hqlp_ij8gceYKo1KVJfWzyT-pV2csGU54zARC-sKkuPhPrFO49eABsjm-2eguzyUa7Al94S4J01RUxeZkfsdOnLoC5HgqfEPsbDaJaX7blA4D8kP-zD7bPRoC4jQEvmFXnwgUAaMj9TfvKieZfgyitZNoFcVzMV--rcVhCnbbULo3IjrsxnJh4jiWa9VesCi8DPaHO8PIHEloOf2fk7b4BDWnz5czo03O0cdtCEz-7r74VHFBmu3HBcTbSOB_tXSGSddNF6W2Uud2k_-SZroaiM2EuvLT94L6oJLFYRvzUapzjMnJif2UAdqWsCpSsM___76QSBXEszWQ27g5oR405IcyOXAMvgdVDdyTMD5CfMx2Ivf93Iui1oIGfpdO5pSPE9aPm8ifm32wnsxIl1rgwrv2QsIM98t5D7CaBiLylsAOCLwhHDNPU80k0zfo5JZH82VSc_NHr_pqYVqIgAFZazNCZXbTr3bxf0aYUC6KO6POQeZcA |website=watermark.silverchair.com}}</ref> ||
 
|-
 
|-
| 1968 || || Scientific development || The idea that vitamin D might function as a steroid-like hormone emerges.<ref name="Torres">{{cite book |last1=Torres |first1=Pablo A. Ureña |last2=Cozzolino |first2=Mario |last3=Vervloet |first3=Marc G. |title=Vitamin D in Chronic Kidney Disease |date=21 September 2016 |publisher=Springer |isbn=978-3-319-32507-1 |url=https://books.google.com.ar/books/about/Vitamin_D_in_Chronic_Kidney_Disease.html?id=xlgeDQAAQBAJ&source=kp_book_description&redir_esc=y |language=en}}</ref>
+
| 1963 || || Recommendation || The US {{w|Food and Drug Administration}}'s Daily Recommended Allowance of vitamin D is determined to be 400 IU, consistent with the recommendations of the American Academy of Pediatrics (AAP) Committee on Nutrition.<ref>{{cite journal |last1=Huh |first1=Susanna Y. |last2=Gordon |first2=Catherine M. |title=Vitamin D deficiency in children and adolescents: Epidemiology, impact and treatment |journal=Reviews in Endocrine and Metabolic Disorders |date=June 2008 |volume=9 |issue=2 |pages=161–170 |doi=10.1007/s11154-007-9072-y}}</ref> || {{w|United States}}
 
|-
 
|-
| 1968–1971 || || || During this period, researchers make great progress in understanding the metabolic processing of vitamin D and its physiological activity.<ref name="Hochberg"/>  
+
| 1963 || || Recommendation || The American Academy of Pediatrics Committee on Nutrition recommends that all infants receive 10μg (400 IU) of vitamin D per day.<ref name="Hochberg"/> || {{w|United States}}
 
|-
 
|-
| 1969 || || Scientific development || The vitamin D receptor (VDR) is discovered in the intestine of vitamin D deficient chicks.<ref name="Torres"/>
+
| 1965–1975 || || Research || In this period, the elements of the vitamin D endocrine system that regulate calcium and phosphorus become clear.<ref>{{cite journal |last1=DeLuca |first1=Hector F |title=History of the discovery of vitamin D and its active metabolites |journal=BoneKEy Reports |date=8 January 2014 |volume=3 |doi=10.1038/bonekey.2013.213}}</ref> ||
 
|-
 
|-
| 1969 || || || The chemical synthesis of 25-0H-D3 is determined by J. W. Blunt and Hector F. DeLuca.<ref name="DeLuca"/><ref>{{cite journal |last1=Blunt |first1=J. W. |last2=DeLuca |first2=Hector F. |title=The synthesis of 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3 |journal=Biochemistry |date=1 February 1969 |volume=8 |issue=2 |pages=671–675 |doi=10.1021/bi00830a031}}</ref> || {{w|United States}}
+
| Mid–1960s || || Research || New techniques using radioactively labeled substances are developed. Before this, scientists did not have the tools to follow vitamin D metabolism in living subjects.<ref name="Hochberg"/>  
 
|-
 
|-
| 1970 || || || “At the time of Lou’s arrival in St. Louis osteoporosis research was pretty much in its infancy. Because techniques of generating authentic bone cells in culture were not in hand, most studies were largely phenomenological. Lou, however, saw the potential of the field and his leadership skills and dynamism enabled him to become its father. His interests were broad but he had a particular passion for vitamin D metabolism and how it relates to the skeleton. When I first met Lou in the early 1970s John Haddad was one of his fellows and together they developed the first assay for serum 25-hydroxyvitamin D. Lou’s had the capacity to consistently visualize his research in the context of patient care and publicize the significance of skeletal disease. He was prolific, publishing in excess of 300 papers and with Steve Krane, “Metabolic Bone Diseases and Related Disorders”. Before Lou Avioli, osteoporosis was a boring entity which did not lend itself to meaningful investigation. Lou saw the big picture.He realized that progress in skeletal research demanded a first-class research society and so in the mid-1970s he convened a committee of leaders in the field to organize the American Society for Bone and Mineral Research”” <ref name="Holimicf">{{cite web |last1=Holick |first1=Michael F. |title=Vitamin D: Physiology, Molecular Biology, and Clinical Applications |url=https://books.google.com.ar/books?id=EhX2sgEACAAJ&dq=vitamin+e+michael&hl=en&sa=X&redir_esc=y |publisher=Humana Press |access-date=16 August 2021 |language=en |date=23 April 2010}}</ref>
+
| 1966 || || Research || Wasserman and his colleagues discover the existence of a calcium-binding protein in the intestines of chicks given vitamin D.<ref name="DeLuca"/> ||
 
|-
 
|-
| 1970 || || Scientific development || The hormonal form of vitamin D ({{w|calcitriol}}) is discovered. This would firmly establish the essential role of the kidney in vitamin D biological actions.<ref name="Holimicf"/>
+
| 1967 || || Research || Loomis suggests that melanin pigmentation evolved for protection from vitamin intoxication because of excessive exposure to sunlight.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1971 || || || {{w|Calcitriol}}, an active form of {{w|vitamin D}}, is identified by American adult endocrinologist {{w|Michael F. Holick}} working in the laboratory of {{w|Hector DeLuca}}.<ref>{{cite journal | vauthors = Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ | title = Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine | journal = Biochemistry | volume = 10 | issue = 14 | pages = 2799–804 | date = July 1971 | pmid = 4326883 | doi = 10.1021/bi00790a023 }}</ref><ref name="pmid4323790">{{cite journal | vauthors = Holick MF, Schnoes HK, DeLuca HF | title = Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 4 | pages = 803–4 | date = April 1971 | pmid = 4323790 | pmc = 389047 | doi = 10.1073/pnas.68.4.803 | bibcode = 1971PNAS...68..803H | doi-access = free }}</ref> || {{w|United States}}
+
| 1968 || || Research || Team led by {{w|Hector DeLuca}} at the {{w|University of Wisconsin}} isolate an active substance identified as 25-hydroxyvitamin D3, which the team later proves to be produced in the {{w|liver}}.<ref name="Hochberg"/> || {{w|United States}}
 
|-
 
|-
| 1971 || || || D. R. Fraser and E. Kodicek first identify the kidney as the source of {{w|calcitriol}}.<ref>{{cite journal |last1=Fraser |first1=D. R. |last2=Kodicek |first2=E. |title=Unique Biosynthesis by Kidney of a Biologically Active Vitamin D Metabolite |journal=Nature |date=November 1970 |volume=228 |issue=5273 |pages=764–766 |doi=10.1038/228764a0}}</ref>
+
| 1968 || {{w|Kidney disease}} || Research || The idea that vitamin D might function as a steroid-like hormone emerges.<ref name="Torres">{{cite book |last1=Torres |first1=Pablo A. Ureña |last2=Cozzolino |first2=Mario |last3=Vervloet |first3=Marc G. |title=Vitamin D in Chronic Kidney Disease |date=21 September 2016 |publisher=Springer |isbn=978-3-319-32507-1 |url=https://books.google.com.ar/books/about/Vitamin_D_in_Chronic_Kidney_Disease.html?id=xlgeDQAAQBAJ&source=kp_book_description&redir_esc=y |language=en}}</ref>
 
|-
 
|-
| 1972 || || || The chemical synthesis of 1α,25-(OH)<sub>2</sub>D<sub>3</sub> ({{w|calcitriol}}) is achieved.<ref name="DeLuca"/>
+
| 1968–1971 || || Research || During this period, researchers make great progress in understanding the metabolic processing of vitamin D and its physiological activity.<ref name="Hochberg"/> ||
 
|-
 
|-
| 1973 || {{w|Rickets}} || || “The earliest description of adolescent rickets and osteomalacia in India was in the early 1990s (10–12). However, Hodgkin et al. in 1973 reported that osteomalacia resulting from vitamin D deficiency was uncommon among Punjabis in India, in contrast with Punjabis in Britain, and this disparity was explained by the difference in sunlight exposure in the two populations” <ref name="Holimicf"/>
+
| 1969 || || Research || The vitamin D receptor (VDR) is discovered in the intestine of vitamin D deficient chicks.<ref name="Torres"/> ||
 
|-
 
|-
| 1974 || || || “In 1974, a vitamin D deficiency in postmenopausal women with rheumatoid arthritis who had suffered fractures compared with postmenopausal women with rheumatoid arthritis who had not suffered fractures was reported” <ref name="Holimicf"/>
+
| 1969 || || Research || The chemical synthesis of {{w|calcifediol}} is determined by J. W. Blunt and Hector F. DeLuca.<ref name="DeLuca"/><ref>{{cite journal |last1=Blunt |first1=J. W. |last2=DeLuca |first2=Hector F. |title=The synthesis of 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3 |journal=Biochemistry |date=1 February 1969 |volume=8 |issue=2 |pages=671–675 |doi=10.1021/bi00830a031}}</ref> || {{w|United States}}
 
|-
 
|-
| 1974 || || || The existence of a chromosomal receptor for vitamin D is demonstrated.<ref name="Hochberg"/>
+
| 1971 || || Research || {{w|Calcitriol}}, an active form of {{w|vitamin D}}, is identified by American adult endocrinologist {{w|Michael F. Holick}} working in the laboratory of {{w|Hector DeLuca}}.<ref>{{cite journal | vauthors = Holick MF, Schnoes HK, DeLuca HF, Suda T, Cousins RJ | title = Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine | journal = Biochemistry | volume = 10 | issue = 14 | pages = 2799–804 | date = July 1971 | pmid = 4326883 | doi = 10.1021/bi00790a023 }}</ref><ref name="pmid4323790">{{cite journal | vauthors = Holick MF, Schnoes HK, DeLuca HF | title = Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 4 | pages = 803–4 | date = April 1971 | pmid = 4323790 | pmc = 389047 | doi = 10.1073/pnas.68.4.803 }}</ref> || {{w|United States}} 
 
|-
 
|-
| 1974 || || || "The possibility that UV light–catalyzed vitamin D3 synthesis might influence MS susceptibility was proposed in 1974"
+
| 1971 || || Research || D. R. Fraser and E. Kodicek first identify the kidney as the source of {{w|calcitriol}}.<ref>{{cite journal |last1=Fraser |first1=D. R. |last2=Kodicek |first2=E. |title=Unique Biosynthesis by Kidney of a Biologically Active Vitamin D Metabolite |journal=Nature |date=November 1970 |volume=228 |issue=5273 |pages=764–766 |doi=10.1038/228764a0}}</ref> ||
 
|-
 
|-
| Early 1970s || || || “The prodrug, 1(OH)D3, was developed in the early 1970s (84, 85) following the discovery of the hormone, 1α,25-(OH)2D3, and the realization that the kidney was the main site of its synthesis” <ref name="Holimicf"/>
+
| 1972 || || Research || The chemical synthesis of 1α,25-(OH)<sub>2</sub>D<sub>3</sub> ({{w|calcitriol}}) is achieved.<ref name="DeLuca"/> ||
 
|-
 
|-
| 1975 || || || “The recommended dose of vitamin D was decreased in steps, and in 1964 the dose was recommended to be reduced from the dose interval of 4,000–5,000 IU down to 2,000 IU/day (37), and in 1975 it was further reduced to 1,000 IU/day.<ref name="Holimicf"/>
+
| 1974 || {{w|Rheumatoid arthritis}} || Research || Researchers report {{w|vitamin D deficiency}} in postmenopausal women with {{w|rheumatoid arthritis}} who have suffered fractures compared with postmenopausal women with rheumatoid arthritis who have not suffered fractures.<ref>{{cite journal |last1=Maddison |first1=P. J. |last2=Bacon |first2=P. A. |title=Vitamin D Deficiency, Spontaneous Fractures, and Osteopenia in Rheumatoid Arthritis |journal=BMJ |date=23 November 1974 |volume=4 |issue=5942 |pages=433–435 |doi=10.1136/bmj.4.5942.433}}</ref> ||
 
|-
 
|-
| 1975 || || Scientific development || Mark Haussler at the University of Arizona discovers a protein receptor that binds calcitriol to the nucleus of cells in the intestine.<ref name="Hochberg"/>
+
| 1974 || || Research || The existence of a chromosomal receptor for vitamin D is demonstrated.<ref name="Hochberg"/> ||
 
|-
 
|-
| 1977 || || Scientific development || A report from the laboratory of Elsie Widdowson in {{w|Cambridge}}, {{w|England}}, describes a new form of water-soluble vitamin D in human milk. This metabolite, vitamin D sulfate, is present at concentrations of 400–950 IU/L. This would prompt the gained credibility of the idea that breast-fed infants do not need supplemental vitamin D.<ref name="Frank R"/> || {{w|United Kingdom}}
+
| 1975 || || Research || Mark Haussler at the University of Arizona discovers a protein receptor that binds {{w|calcitriol}} to the nucleus of cells in the intestine.<ref name="Hochberg"/><ref>{{cite journal |last1=Brumbaugh |first1=PF |last2=Haussler |first2=MR |title=Specific binding of 1alpha,25-dihydroxycholecalciferol to nuclear components of chick intestine. |journal=The Journal of biological chemistry |date=25 February 1975 |volume=250 |issue=4 |pages=1588-94 |pmid=163254}}</ref> || {{w|United States}}
 
|-
 
|-
| 1978 || {{w|Rickets}} || || “In 1978, Pettifor and colleagues described what they believed to be dietary calcium deficiency rickets in children living in a rural community in South Africa” <ref name="Holimicf"/>
+
| 1977 || || Research || A report from the laboratory of Elsie Widdowson in {{w|Cambridge}}, {{w|England}}, describes a new form of water-soluble vitamin D in human milk. This metabolite, vitamin D sulfate, is present at concentrations of 400–950 IU/L. This would prompt the gained credibility of the idea that breast-fed infants do not need supplemental vitamin D.<ref name="Frank R"/> || {{w|United Kingdom}}
 
|-
 
|-
| 1980 || {{w|Rickets}} || || “The physiological importance of VDR localization became first apparent in the late 1980s, when we traced back the reason for hereditary vitamin D-resistant rickets in two families to the inability of the receptor to translocate from the cytoplasm to the nucleus” <ref name="Holimicf"/>
+
| 1979 || || Literature || Anthony W. Norman publishes ''Vitamin D: The Calcium Homeostatic Steroid Hormone''.<ref>{{cite book |last1=Norman |first1=Anthony W. |title=Vitamin D: The Calcium Homeostatic Steroid Hormone |date=1979 |publisher=Academic Press |isbn=978-0-12-521050-8 |url=https://books.google.com.ar/books/about/Vitamin_D.html?id=wiJrAAAAMAAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1980 || || || "The exact sequence of steps leading to the photoproduction of cholecalciferol in the skin were reported in a comprehensive paper by Holick et al."<ref name="Wolfv"/><ref>{{cite journal |last1=Holick |first1=M. |last2=MacLaughlin |first2=J. |last3=Clark |first3=M. |last4=Holick |first4=S. |last5=Potts |first5=J. |last6=Anderson |first6=R. |last7=Blank |first7=I. |last8=Parrish |first8=J. |last9=Elias |first9=P |title=Photosynthesis of previtamin D3 in human skin and the physiologic consequences |journal=Science |date=10 October 1980 |volume=210 |issue=4466 |pages=203–205 |doi=10.1126/science.6251551}}</ref> || {{w|United States}}
+
| 1980 || || Research || Holick et al. report on the exact sequence of steps leading to the photoproduction of {{w|cholecalciferol}} in the skin.<ref name="Wolfv"/><ref>{{cite journal |last1=Holick |first1=M. |last2=MacLaughlin |first2=J. |last3=Clark |first3=M. |last4=Holick |first4=S. |last5=Potts |first5=J. |last6=Anderson |first6=R. |last7=Blank |first7=I. |last8=Parrish |first8=J. |last9=Elias |first9=P |title=Photosynthesis of previtamin D3 in human skin and the physiologic consequences |journal=Science |date=10 October 1980 |volume=210 |issue=4466 |pages=203–205 |doi=10.1126/science.6251551}}</ref> || {{w|United States}}
 
|-  
 
|-  
| 1980 || Short gestation and low birth weight || Scientific development || In response to recognition of a high incidence of pregnancy-associated osteomalacia and decreased fetal size in association with vitamin D deficiency among Asian (primarily Indian) women in England, O.G. Brooke et al. evaluate vitamin D supplementation in Asian women. The study includes 59 pregnant women given 1,000 IU/day in their last trimester and a matched group of 67 women given placebo. The researchers report modest increase in birth weight of 123 g in the treatment group.<ref>{{cite journal |last1=Brooke |first1=O G |last2=Brown |first2=I R |last3=Bone |first3=C D |last4=Carter |first4=N D |last5=Cleeve |first5=H J |last6=Maxwell |first6=J D |last7=Robinson |first7=V P |last8=Winder |first8=S M |title=Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. |journal=BMJ |date=15 March 1980 |volume=280 |issue=6216 |pages=751–754 |doi=10.1136/bmj.280.6216.751}}</ref> || {{w|United Kingdom}}
+
| 1980 || Short gestation and low birth weight || Research || In response to recognition of a high incidence of pregnancy-associated osteomalacia and decreased fetal size in association with vitamin D deficiency among Asian (primarily Indian) women in England, O.G. Brooke et al. evaluate vitamin D supplementation in Asian women. The study includes 59 pregnant women given 1,000 IU/day in their last trimester and a matched group of 67 women given placebo. The researchers report modest increase in birth weight of 123 g in the treatment group.<ref>{{cite journal |last1=Brooke |first1=O G |last2=Brown |first2=I R |last3=Bone |first3=C D |last4=Carter |first4=N D |last5=Cleeve |first5=H J |last6=Maxwell |first6=J D |last7=Robinson |first7=V P |last8=Winder |first8=S M |title=Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. |journal=BMJ |date=15 March 1980 |volume=280 |issue=6216 |pages=751–754 |doi=10.1136/bmj.280.6216.751}}</ref> || {{w|United Kingdom}}
|-
 
| 1980 || {{w|Cancer}} || || The solar UVB/vitamin D/cancer theory is proposed by Cedric and Frank Garland. The researchers hypothesize that the potential benefit of sun exposure is attributed to vitamin D. Initially, the hypothesis is centered on {{w|colon cancer}}, but later it is extended to {{w|breast cancer}}, {{w|ovarian cancer}}, {{w|prostate cancer}}, and to multiple cancer types.<ref name="Reichrath">{{cite book |last1=Reichrath |first1=Jörg |title=Sunlight, Vitamin D and Skin Cancer |date=11 September 2020 |publisher=Springer Nature |isbn=978-3-030-46227-7 |url=https://books.google.com.ar/books?id=lqT8DwAAQBAJ&printsec=frontcover&dq=Sunlight,+Vitamin+D+and+Skin+Cancer+reichrath&hl=en&sa=X&redir_esc=y#v=onepage&q=Sunlight%2C%20Vitamin%20D%20and%20Skin%20Cancer%20reichrath&f=false |language=en}}</ref>
 
|-
 
| 1980 || || || “Marya et al. (27) studied 25 women treated with 1,200 IU of vitamin D a day in their third trimester, 20 women treated with two doses of 600,000 IU in the seventh and eighth months of pregnancy, and 75 women who received no supplemental vitamin D in a study published in 1980” <ref name="Holimicf"/>
 
|-
 
| 1980 || {{w|Cancer}} || || “One of the first epidemiological investigations on the association between vitamin D deficiency and cancer mortality was published by Garland et al. in 1980 (6). The authors found a clear positive association between latitude and mortality from colon cancer in the United States” <ref name="Holimicf"/>
 
|-
 
| 1980 || {{w|Cancer}} || || “This potential anticancer property of sun exposure was largely ignored for about four decades, until the early 1980s when Garland and Garland hypothesized that poor vitamin D status from lower solar UVB radiation exposure explained the association between higher latitudes and increased mortality of a number of cancers, including colon cancer (3), breast cancer (4), and ovarian cancer” <ref name="Holimicf"/> “Several years afterward, Applerly reported an inverse association between latitude and cancer mortality rates (2). These observations led to the hypothesis that skin cancer somehow conferred immunity for other cancers. Surprisingly, no one seems to have explored the mechanism of this effect until 1980 when Garland and Garland proposed that the apparent benefit of sunlight exposure was mediated by vitamin D” <ref name="Holimicf"/>
 
|-
 
| 1980 || {{w|Cancer}} ([[w:colon cancer|colon]]) || || C. F. Garland and F. C. Garland publish a seminal article on the relationship between vitamin D, calcium and colon cancer risk in the International Journal of Epidemiology. In this ecologic analysis, they propose that vitamin D and {{w|calcium}} are protective factors against {{w|colon cancer}}.<ref name="Mohrv"/><ref>{{cite journal |last1=Garland |first1=Cedric F |last2=Garland |first2=Frank C |title=Do Sunlight and Vitamin D Reduce the Likelihood of Colon Cancer? |journal=International Journal of Epidemiology |date=1980 |volume=9 |issue=3 |pages=227–231 |doi=10.1093/ije/9.3.227}}</ref> ||
 
|-
 
| 1980 || {{w|Cancer}} ([[w:colon cancer|colon]]) || || Cedric and Frank Garland of Johns Hopkins University report a strong latitudinal gradient for colon cancer mortality rates, and hypothesize that higher levels of vitamin D compounds in the serum of people in the south are responsible, and that calcium intake also would reduce incidence.<ref name="Mohrv"/> || {{w|United States}}
 
|-
 
| 1980 || || Scientific development || {{w|Michael F. Holick}} describes the dermal synthesis of vitamin D.<ref name="Wageningen">{{cite book |title=Handbook of vitamin D in human health : prevention, treatment and toxicity |date=2013 |publisher=Wageningen Academic Publishers |location=Wageningen |isbn=978-90-8686-765-3}}</ref> || {{w|United States}}
 
|-
 
| 1981 || || || “Four trials have compared daily vitamin D supplementation at doses of 400 IU/day (46) and 1,000 IU/day (47–49) versus placebo. One limitation of these evaluations is the restricted effect of 400–1,000 IU/day on serum 25(OH)D concentrations. Table 1 shows serum 25(OH)D changes from baseline to the end of pregnancy of trials that reported maternal 25(OH)D. One trial, first published in 1981, exhibited a mean increase in serum 25(OH)D of 59.1 ng/ml with a dose of 1,000 IU/day vitamin D” <ref name="Holimicf"/>
 
|-
 
| 1981 || {{w|Cardiovascular disease}} || Scientific development || Drawing on ecological studies of variations in cardiovascular disease by season, latitude, and altitude, Robert Scragg publishes a hypothesis that sunlight and vitamin D may protect against cardiovascular disease.<ref>{{cite journal |last1=Scragg |first1=Robert |title=Seasonality of Cardiovascular Disease Mortality and the Possible Protective Effect of Ultra-violet Radiation |journal=International Journal of Epidemiology |date=1981 |volume=10 |issue=4 |pages=337–341 |doi=10.1093/ije/10.4.337}}</ref> || {{w|Australia}}
 
|-
 
| 1981 || {{w|Cancer}} ({{w|melanoma}}, {{w|leukemia}}) || Scientific development || The classical consideration of vitamin D as a regulator of calcium and phosphate metabolism and bone biology begins when David Feldman’s<ref>{{cite journal |last1=Colston |first1=Kay |last2=Colston |first2=M. Joseph |last3=Feldman |first3=David |title=1,25-DIHYDROXYVITAMIN D 3 AND MALIGNANT MELANOMA: THE PRESENCE OF RECEPTORS AND INHIBITION OF CELL GROWTH IN CULTURE |journal=Endocrinology |date=March 1981 |volume=108 |issue=3 |pages=1083–1086 |doi=10.1210/endo-108-3-1083}}</ref> and Tatsuo Suda’s<ref>{{cite journal |last1=Abe |first1=E. |last2=Miyaura |first2=C. |last3=Sakagami |first3=H. |last4=Takeda |first4=M. |last5=Konno |first5=K. |last6=Yamazaki |first6=T. |last7=Yoshiki |first7=S. |last8=Suda |first8=T. |title=Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. |journal=Proceedings of the National Academy of Sciences |date=1 August 1981 |volume=78 |issue=8 |pages=4990–4994 |doi=10.1073/pnas.78.8.4990}}</ref> groups show that the most active vitamin D metabolite, {{w|calcitriol}}, inhibits the proliferation of melanoma cells and induces the differentiation of leukemic cells.<ref name="Holimicf"/> ||
 
|-
 
| 1981 || {{w|Cystic fibrosis}} || Scientific development || Reduced vitamin D binding protein levels in people with {{w|cystic fibrosis}} is first reported.<ref name="Litonjua"/>
 
|-
 
| 1982 || {{w|Rickets}} || Scientific development || The role of the vitamin D receptor in vitamin D-dependent rickets type-2 is realized.<ref name="Hochberg"/>
 
|-
 
| 1983 || || Scientific development || S. H. Sedrani et al. find unexpectedly low vitamin D levels in Saudi university students as well as in elderly subjects suggesting that up to 100% of the Saudi population may have vitamin D deficiency or insufficiency.<ref>{{cite journal |last1=Sedrani |first1=S H |last2=Elidrissy |first2=A W |last3=El Arabi |first3=K M |title=Sunlight and vitamin D status in normal Saudi subjects |journal=The American Journal of Clinical Nutrition |date=1 July 1983 |volume=38 |issue=1 |pages=129–132 |doi=10.1093/ajcn/38.1.129}}</ref> || {{w|Saudi Arabia}}
 
|-
 
| 1984 || || || “In 1984, Greer et al. (88) exposed lactating white women to UVB exposure equivalent to 30 min of sunshine at midday on a clear summer day at temperate latitudes” <ref name="Holimicf"/>
 
 
|-
 
|-
| 1984 || || || Conclusive evidence of the importance of correcting the impaired 25(OH)D availability in chronic kidney disease is reported. <ref name="Holimicf"/>
+
| 1980 || {{w|Cancer}} || Research (theory) || The solar UVB/vitamin D/cancer theory is proposed by brothers {{w|Cedric Garland}} and {{w|Frank C. Garland}}. The researchers hypothesize that the potential benefit of sun exposure is attributed to vitamin D. Initially, the hypothesis is centered on {{w|colon cancer}}, but later it is extended to {{w|breast cancer}}, {{w|ovarian cancer}}, {{w|prostate cancer}}, and to multiple cancer types.<ref name="Reichrath">{{cite book |last1=Reichrath |first1=Jörg |title=Sunlight, Vitamin D and Skin Cancer |date=11 September 2020 |publisher=Springer Nature |isbn=978-3-030-46227-7 |url=https://books.google.com.ar/books?id=lqT8DwAAQBAJ&printsec=frontcover&dq=Sunlight,+Vitamin+D+and+Skin+Cancer+reichrath&hl=en&sa=X&redir_esc=y#v=onepage&q=Sunlight%2C%20Vitamin%20D%20and%20Skin%20Cancer%20reichrath&f=false |language=en}}</ref> || {{w|United States}}
 
|-
 
|-
| 1984 || || || “In 1984, Greer et al. (88) exposed lactating white women to UVB exposure equivalent to 30 min of sunshine at midday on a clear summer day at temperate latitudes. With this exposure, the vitamin D content of the milk significantly increased with a peak at 48 h and with a return to baseline at 7 days” <ref name="Holimicf"/>
+
| 1980 || {{w|Hypocalcemia}}, secondary {{w|hyperparathyroidism}}, {{w|osteodystrophy}}, {{w|rickets}}, {{w|osteomalacia}} || Drug launch || Alfacalcidol is first introduced in Canada. It is a vitamin D analogue used for the management of hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in patients with chronic renal failure, as well as some types of rickets and osteomalacia.<ref>{{cite web |title=Alfacalcidol |url=https://go.drugbank.com/drugs/DB01436 |website=go.drugbank.com |access-date=23 September 2021}}</ref> || {{w|Canada}}
 
|-
 
|-
| 1984 || || || A paper by Narang et al. states that 2,400 IU/day is the dose of vitamin D that statistically increases serum calcium, but not quite into the {{w|hypercalcemia}} range.<ref name="Holimicf"/>
+
| 1980 || Birth weight || Research || R. K. Marya et al. study 25 pregnant women treated with 1,200 IU of vitamin D a day in their third trimester, 20 women treated with two doses of 600,000 IU in the seventh and eighth months of pregnancy, and 75 women who received no supplemental vitamin D. The researchers report a significantly greater increase in birth weight with either vitamin D supplementation, but greater increase with the 600,000 IU doses.<ref>{{cite journal |last1=Marya |first1=R.K. |last2=Rathee |first2=S. |last3=Lata |first3=V. |last4=Mudgil |first4=S. |title=Effects of Vitamin D Supplementation in Pregnancy |journal=Gynecologic and Obstetric Investigation |date=1981 |volume=12 |issue=3 |pages=155–161 |doi=10.1159/000299597}}</ref> ||
 
|-
 
|-
| 1985 || || || A study reports that of 40 Indonesian patients with active {{w|tuberculosis}} and treated with anti-tuberculosis chemotherapy, 10 patients with the highest Calcifediol levels at the outset of therapy had “less active pulmonary disease”.<ref name="Litonjua"/>
+
| 1980 || {{w|Cancer}} ([[w:colon cancer|colon]]) || Research || C. F. Garland and F. C. Garland publish a seminal article on the relationship between vitamin D, calcium and colon cancer risk in the International Journal of Epidemiology. In this ecologic analysis, they propose that vitamin D and {{w|calcium}} are protective factors against {{w|colon cancer}}.<ref name="Mohrv"/> The authors also find a clear positive association between latitude and mortality from colon cancer in the United States. They hypothesize that this might be related to sun-induced vitamin D.<ref>{{cite journal |last1=Garland |first1=Cedric F |last2=Garland |first2=Frank C |title=Do Sunlight and Vitamin D Reduce the Likelihood of Colon Cancer? |journal=International Journal of Epidemiology |date=1980 |volume=9 |issue=3 |pages=227–231 |doi=10.1093/ije/9.3.227}}</ref> || {{w|United States}}
 
|-
 
|-
| 1985 || {{w|Cancer}} ([[w:colorectal cancer|colorectal]]) || || “This hypothesis gained strong support when Garland et al. (2) in 1985 published the results of a 19-year prospective trial, showing that low dietary intakes of vitamin D and of calcium are associated with a significant risk of colorectal cancer” <ref name="Holimicf"/>
+
| 1980 || || Research || {{w|Michael F. Holick}} describes the dermal synthesis of vitamin D.<ref name="Wageningen">{{cite book |title=Handbook of vitamin D in human health : prevention, treatment and toxicity |date=2013 |publisher=Wageningen Academic Publishers |location=Wageningen |isbn=978-90-8686-765-3}}</ref> || {{w|United States}}
 
|-
 
|-
| 1985 || || || Davies observes that people migrating to the United Kingdom from countries with a high incidence of latent ''{{w|Mycobacterium tuberculosis}}'' infection experience rates of active tuberculosis that exceeds rates in their countries of origin, and that this increased risk coincide with the development of vitamin D deficiency, probably arising as a result of decreased sun exposure.<ref name="Litonjua"/>
+
| 1981 || {{w|Cardiovascular disease}} || Research || Drawing on ecological studies of variations in cardiovascular disease by season, latitude, and altitude, Robert Scragg publishes a hypothesis that sunlight and vitamin D may protect against cardiovascular disease.<ref>{{cite journal |last1=Scragg |first1=Robert |title=Seasonality of Cardiovascular Disease Mortality and the Possible Protective Effect of Ultra-violet Radiation |journal=International Journal of Epidemiology |date=1981 |volume=10 |issue=4 |pages=337–341 |doi=10.1093/ije/10.4.337}}</ref> || {{w|Australia}}
 
|-
 
|-
| 1985 || {{w|Psoriasis}} || || S. Morimoto and Y. Kumahara report that a patient who was treated orally with 1α-hydroxyvitamin D3 for osteoporosis had a dramatic remission of psoriatic skin lesions.<ref>{{cite journal |last1=Morimoto |first1=S |last2=Kumahara |first2=Y |title=A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3. |journal=Medical journal of Osaka University |date=March 1985 |volume=35 |issue=3-4 |pages=51-4 |pmid=4069059}}</ref> || {{w|Japan}} ({{w|Osaka University}})
+
| 1981 || {{w|Cancer}} ({{w|melanoma}}, {{w|leukemia}}) || Research || The classical consideration of vitamin D as a regulator of calcium and phosphate metabolism and bone biology begins when David Feldman’s<ref>{{cite journal |last1=Colston |first1=Kay |last2=Colston |first2=M. Joseph |last3=Feldman |first3=David |title=1,25-DIHYDROXYVITAMIN D 3 AND MALIGNANT MELANOMA: THE PRESENCE OF RECEPTORS AND INHIBITION OF CELL GROWTH IN CULTURE |journal=Endocrinology |date=March 1981 |volume=108 |issue=3 |pages=1083–1086 |doi=10.1210/endo-108-3-1083}}</ref> and Tatsuo Suda’s<ref>{{cite journal |last1=Abe |first1=E. |last2=Miyaura |first2=C. |last3=Sakagami |first3=H. |last4=Takeda |first4=M. |last5=Konno |first5=K. |last6=Yamazaki |first6=T. |last7=Yoshiki |first7=S. |last8=Suda |first8=T. |title=Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. |journal=Proceedings of the National Academy of Sciences |date=1 August 1981 |volume=78 |issue=8 |pages=4990–4994 |doi=10.1073/pnas.78.8.4990}}</ref> groups show that the most active vitamin D metabolite, {{w|calcitriol}}, inhibits the proliferation of melanoma cells and induces the differentiation of leukemic cells.<ref name="Holimicf"/> ||  
 
|-
 
|-
| 1986 || || || “Insight into vitamin D-induced antimicrobial activity by human monocytes and macrophages against M. tuberculosis was first suggested by experiments in the labs of Rook in 1986 (45) and Crowle in 1987” <ref name="Holimicf"/>
+
| 1981 || {{w|Cystic fibrosis}} || Research || Reduced vitamin D binding protein levels in people with {{w|cystic fibrosis}} is first reported.<ref name="Litonjua"/> ||
 
|-
 
|-
| 1986 || || || “In 1986, a Finnish trial compared 15 weeks of maternal vitamin D3 intake of 1,000 or 2,000 IU/day with infant intake of 400 IU/day and demonstrated healthy infant vitamin D status achieved in the 2,000 IU/day maternal intake group and the 400 IU/day infant intake group with mean serum 25(OH)D around 30 ng/ml” <ref name="Holimicf"/>
+
| 1982 || {{w|Rickets}} || Research || The role of the vitamin D receptor in vitamin D-dependent rickets type-2 is realized.<ref name="Hochberg"/> ||
 
|-
 
|-
| 1986 || {{w|Cancer}} ({{w|melanoma}}, {{w|leukemia}}) || || Colston et al. become the first to demonstrate that 1α,25(OH)2D3 inhibits human {{w|melanoma}} cell proliferation significantly in vitro at nanomolar concentrations. Parallel studies in the same year also find that 1α25(OH)2D3 could induce differentiation in cultured mouse and human myeloid {{w|leukemia}} cells.<ref name="Gombart">{{cite book |last1=Gombart |first1=Adrian F. |title=Vitamin D: Oxidative Stress, Immunity, and Aging |date=21 November 2012 |publisher=CRC Press |isbn=978-1-4398-5021-3 |url=https://books.google.com.ar/books?id=1CfOBQAAQBAJ&printsec=frontcover&dq=vitamin+d+gombart&hl=en&sa=X&redir_esc=y#v=onepage&q=vitamin%20d%20gombart&f=false |language=en}}</ref> ||
+
| 1983 || || Research || S. H. Sedrani et al. find unexpectedly low vitamin D levels in Saudi university students as well as in elderly subjects suggesting that up to 100% of the Saudi population may have vitamin D deficiency or insufficiency.<ref>{{cite journal |last1=Sedrani |first1=S H |last2=Elidrissy |first2=A W |last3=El Arabi |first3=K M |title=Sunlight and vitamin D status in normal Saudi subjects |journal=The American Journal of Clinical Nutrition |date=1 July 1983 |volume=38 |issue=1 |pages=129–132 |doi=10.1093/ajcn/38.1.129}}</ref> || {{w|Saudi Arabia}}
 
|-
 
|-
| 1986 || {{w|Cancer}} ([[w:colorectal cancer|colorectal]]) || || “For colorectal cancer, based on 691 cases diagnosed from 1986 to 2000, a 25 nmol/l (10 ng/ml) increment in 25(OH)D was associated with a reduced risk (multivariate RR=0.63, 95% CI = 0.48–0.83). This association persisted after controlling for body mass index or physical activity, which are contributors to the 25(OH)D score” <ref name="Holimicf"/>
+
| 1984 || Kidney disease || Research || Research by B. P. Halloran et al. reports conclusive evidence of the importance of correcting the impaired 25(OH)D availability in chronic kidney disease.<ref>{{cite journal |last1=Halloran |first1=Bernard P. |last2=Schaefer |first2=Phillip |last3=Lifschitz |first3=Meyer |last4=Levens |first4=Marilyn |last5=Goldsmith |first5=Ralph S. |title=Plasma Vitamin D Metabolite Concentrations in Chronic Renal Failure: Effect of Oral Administration of 25-Hydroxyvitamin D3* |journal=The Journal of Clinical Endocrinology & Metabolism |date=December 1984 |volume=59 |issue=6 |pages=1063–1069 |doi=10.1210/jcem-59-6-1063}}</ref> ||
 
|-
 
|-
| 1986–2000 || {{w|Cancer}} ([[w:colorectal cancer|colorectal]]) || || “For colorectal cancer, based on 691 cases diagnosed from 1986 to 2000, a 25 nmol/l (10 ng/ml) increment in 25(OH)D was associated with a reduced risk (multivariate RR=0.63, 95% CI = 0.48–0.83)<ref name="Holimicf"/>
+
| 1984 || {{w|Breastfeeding}} || Research || In a study, Greer et al. expose lactating white women to UVB exposure equivalent to 30 min of sunshine at midday on a clear summer day at temperate latitudes. With this exposure, the vitamin D content of the milk significantly increases with a peak at 48 h and with a return to baseline at 7 days.<ref>{{cite journal |last1=Greer |first1=Frank R. |last2=Hollis |first2=Bruce W. |last3=Cripps |first3=Derek J. |last4=Tsang |first4=Reginald C. |title=Effects of maternal ultraviolet B irradiation on vitamin D content of human milk |journal=The Journal of Pediatrics |date=September 1984 |volume=105 |issue=3 |pages=431–433 |doi=10.1016/s0022-3476(84)80021-9}}</ref> ||
 
|-
 
|-
| 1987 || || || Molecular cloning of the cDNA encoding chick vitamin D receptor is achieved for the first time by McDonnell et al.<ref name="Hochberg"/>
+
| 1984 || || Research || A paper by Narang et al. states that 2,400 IU/day is the dose of vitamin D that statistically increases serum calcium, but not quite into the {{w|hypercalcemia}} range.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1988 || || || The successful cloning of the cDNA encoding the human vitamin D receptor is achieved.<ref name="Hochberg"/>
+
| 1985 || {{w|Tuberculosis}}, pulmonary disease || Research || A study conducted on 40 Indonesian patients with active {{w|tuberculosis}} and treated with anti-tuberculosis chemotherapy, reports that 10 patients with the highest {{w|calcifediol}} levels at the outset of therapy had “less active pulmonary disease”.<ref name="Litonjua"/> || {{w|Indonesia}}
 
|-
 
|-
| 1988 || || || “Looker et al (78) reported from the National Health and Nutrition examination surveys, a comparison of blood levels of 25(OH)D from 1988, 1994 when compared to data collected from 2000 to 2004 revealed aged adjusted mean serum 25(OH)D levels were 2–8 ng/ml lower in NHANES 2000–2004 than NHANES III. Both children and adults in Australia who have either avoided sun exposure or always wore sun protection have now reported to be at risk of vitamin D deficiency” <ref name="Holimicf"/>
+
| 1985 || {{w|Tuberculosis}} || Research || Davies observes that people migrating to the United Kingdom from countries with a high incidence of latent ''{{w|Mycobacterium tuberculosis}}'' infection experience rates of active tuberculosis that exceeds rates in their countries of origin, and that this increased risk coincide with the development of {{w|vitamin D deficiency}}, probably arising as a result of decreased sun exposure.<ref name="Litonjua"/> || {{w|United Kingdom}}
 
|-
 
|-
| 1988 || || || “Specker (30), in her review of studies of maternal and neonatal outcomes in vitamin D deficiency, reports on a study by Marya et al. (31), published in 1988” <ref name="Holimicf"/>
+
| 1985 || {{w|Psoriasis}} || Research || S. Morimoto and Y. Kumahara report that a patient who was treated orally with 1α-hydroxyvitamin D3 for osteoporosis had a dramatic remission of psoriatic skin lesions.<ref>{{cite journal |last1=Morimoto |first1=S |last2=Kumahara |first2=Y |title=A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3. |journal=Medical journal of Osaka University |date=March 1985 |volume=35 |issue=3-4 |pages=51-4 |pmid=4069059}}</ref> || {{w|Japan}} ({{w|Osaka University}})
 
|-
 
|-
| 1988 || || || The group of {{w|Bert W. O'Malley}} from California Biotechnology Inc. clones the vitamin D receptor.<ref name="Hochberg"/>
+
| 1986 || ''{{w|Mycobacterium tuberculosis}}'' || Research || Experiments by Rook become the first to suggest vitamin D-induced antimicrobial activity by human monocytes and macrophages against ''Mycobacterium tuberculosis''.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1988–1994 || || || “Melamed et al. (41) reviewed NHANES III data of 13,331 adults ≥20 years. 25(OH)D levels were collected from 1988 through 1994, and individuals were followed for mortality through 2000” <ref name="Holimicf"/>
+
| 1986 || {{w|Cancer}} ({{w|melanoma}}, {{w|leukemia}}) || Research || Colston et al. become the first to demonstrate that 1α,25(OH)2D3 ({{w|calcitriol}}) inhibits human {{w|melanoma}} cell proliferation significantly in vitro at nanomolar concentrations. Parallel studies in the same year also find that 1α25(OH)2D3 could induce differentiation in cultured mouse and human myeloid {{w|leukemia}} cells.<ref name="Gombart">{{cite book |last1=Gombart |first1=Adrian F. |title=Vitamin D: Oxidative Stress, Immunity, and Aging |date=21 November 2012 |publisher=CRC Press |isbn=978-1-4398-5021-3 |url=https://books.google.com.ar/books?id=1CfOBQAAQBAJ&printsec=frontcover&dq=vitamin+d+gombart&hl=en&sa=X&redir_esc=y#v=onepage&q=vitamin%20d%20gombart&f=false |language=en}}</ref> ||
 
|-
 
|-
| 1988–2000 || {{w|Cancer}} ([[w:colorectal cancer|colorectal]]) || || “The association between 25(OH)D and colorectal cancer was examined in 16,818 participants followed from 1988–1994 to 2000 in the Third National Health and Nutrition Examination Survey” <ref name="Holimicf"/>
+
| 1987 || || Research || Molecular cloning of the cDNA encoding chick vitamin D receptor is achieved for the first time by McDonnell et al.<ref name="Hochberg"/> ||
 
|-
 
|-
| 1989 || || || {{w|Paricalcitol}} is patented and approved for medical use.<ref name="sad">{{cite book |last1=Fischer |first1=János |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |url=https://books.google.com.ar/books?id=FjKfqkaKkAAC&pg=PA451&redir_esc=y#v=onepage&q&f=false |language=en}}</ref>
+
| 1988 || || Research || The successful cloning of the cDNA encoding the human vitamin D receptor is achieved.<ref name="Hochberg"/> ||
 
|-
 
|-
| 1989 || || || “DEQAS (Vitamin D External Quality Assessment Scheme) was founded in 1989 to compare the performance of assays for vitamin D measurement. It is currently the dominant proficiency testing scheme with more than 470 laboratories participating from over 30 countries” <ref name="Holimicf"/>
+
| 1988 || || Research || A research group led by {{w|Bert W. O'Malley}} from California Biotechnology Inc. manages to clone the vitamin D receptor.<ref name="Hochberg"/> || {{w|United States}}
 
|-
 
|-
| 1989 || {{w|Cancer}} ([[w:colon cancer|colon]]) || || E.D. Gorham et al. postulate an association between ultraviolet-B blocking air pollution and increased risk of breast and colon cancer, based on inhibition by sulfurrelated air pollution of cutaneous vitamin D photosynthesis, resulting in vitamin D deficiency.<ref>{{cite journal |last1=Gorham |first1=ED |last2=Garland |first2=CF |last3=Garland |first3=FC |title=Acid haze air pollution and breast and colon cancer mortality in 20 Canadian cities. |journal=Canadian journal of public health = Revue canadienne de sante publique |date=March 1989 |volume=80 |issue=2 |pages=96-100 |pmid=2720547}}</ref><ref name="Mohrv"/> ||
+
| 1989 || {{w|Kidney disease}} ({{w|hyperparathyroidism}}) || Drug launch || {{w|Paricalcitol}} is patented. It is an [[w:analog (chemistry)|analog]] of 1,25-dihydroxyergocalciferol, the active form of [[w:Vitamin D2|vitamin D<sub>2</sub>]] (ergocalciferol).<ref name="sad">{{cite book |last1=Fischer |first1=János |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |url=https://books.google.com.ar/books?id=FjKfqkaKkAAC&pg=PA451&redir_esc=y#v=onepage&q&f=false |language=en}}</ref> It is a vitamin D analog used to treat hyperparathyroidism associated with stage 3 or greater chronic kidney disease.<ref>{{cite web |title=Paricalcitol |url=https://go.drugbank.com/drugs/DB00910 |website=go.drugbank.com |access-date=21 September 2021}}</ref> || {{w|United States}}
 
|-
 
|-
| 1989 || || || The sequence elements in the human osteocalcin gene conferring basal activation and inducible response of this gene promoter to hormonal 1,25(OH) 2 D 3 are described.<ref name="Torres"/>
+
| 1989 || || Program launch || DEQAS (Vitamin D External Quality Assessment Scheme) is launched to compare the performance of assays for vitamin D measurement. It monitors the performance of 25-hydroxyvitamin D (25-OHD) and 1,25- dihydroxyvitamin D (1,25(OH)2D) assays.<ref>{{cite journal |last1=Carter |first1=G.D. |last2=Berry |first2=J. |last3=Durazo-Arvizu |first3=R. |last4=Gunter |first4=E. |last5=Jones |first5=G. |last6=Jones |first6=J. |last7=Makin |first7=H.L.J |last8=Pattni |first8=P. |last9=Phinney |first9=K.W. |last10=Sempos |first10=C.T. |last11=Williams |first11=E.L. |title=Quality assessment of vitamin D metabolite assays used by clinical and research laboratories |journal=The Journal of Steroid Biochemistry and Molecular Biology |date=October 2017 |volume=173 |pages=100–104 |doi=10.1016/j.jsbmb.2017.03.010}}</ref> DEQAS would grow to be the dominant proficiency testing scheme with more than 470 laboratories participating from over 30 countries.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1989 || || || “The US Recommended Dietary Allowance (RDA) of vitamin D from 1989 is 200 IU (60). However, several investigations have convincingly shown that 200 IU/day has no effect on bone status (61). It has been recommended that adults may need, at a minimum, five times the RDA, or 1,000 IU, to adequately prevent bone frac�tures, protect against some malignancies, and derive other broad-ranging health benefits (60). In conclusion, the 1989 RDA of 200 IU is antiquated, and the newer 600 IU daily reference intake (DRI) dose for adults older than 70 is still not sufficient (60).<ref name="Holimicf"/>
+
| 1989 || {{w|Cancer}} ([[w:breast cancer|breast]] and [[w:colon cancer|colon]]) || Research || E.D. Gorham et al. postulate an association between ultraviolet-B blocking air pollution and increased risk of breast and colon cancer, based on inhibition by sulfurrelated air pollution of cutaneous vitamin D photosynthesis, resulting in vitamin D deficiency.<ref>{{cite journal |last1=Gorham |first1=ED |last2=Garland |first2=CF |last3=Garland |first3=FC |title=Acid haze air pollution and breast and colon cancer mortality in 20 Canadian cities. |journal=Canadian journal of public health = Revue canadienne de sante publique |date=March 1989 |volume=80 |issue=2 |pages=96-100 |pmid=2720547}}</ref><ref name="Mohrv"/> ||
 
|-
 
|-
| 1989 || {{w|Cancer}} ([[w:colon cancer|colon]]) || || Garland et al. report that prediagnostic serum 25(OH)D concentration inversely correlates with colon cancer.<ref name="Wageningen"/>
+
| 1989 || || Research || The sequence elements in the human {{w|osteocalcin}} gene conferring basal activation and inducible response of this gene promoter to hormonal 1,25(OH) 2 D 3 are described.<ref name="Torres"/> ||
 
|-
 
|-
| 1980s || || || “Ligand-binding assays for the vitamin D content in human milk, developed in the 1980s, demonstrate that 30% of the maternal circulating vitamin D and 1% of the maternal circulating 25(OH)D are present” <ref name="Holimicf"/>
+
| 1989 || || Recommendation || The US Recommended Dietary Allowance (RDA) of vitamin D is determined at 200 IU to guarantee a protecting effect against malignancies and other diseases. However, several subsequent investigations would show that 200 IU/day has no effect on bone status, with adults needing five times the RDA, or 1,000 IU, to adequately prevent bone fractures, protect against some malignancies, and derive other broad-ranging health benefits.<ref name="Holimicf"/> || {{w|United States}}
 
|-
 
|-
| 1980s || || || “Design of ligand-binding assays to measure the vitamin D content of human milk in the 1980s prompted the first evaluations of the effect of maternal supplementation” <ref name="Holimicf"/>
+
| 1989 || {{w|Cancer}} ([[w:colon cancer|colon]]) || Research || Garland et al. report that prediagnostic serum 25(OH)D concentration inversely correlates with colon cancer.<ref name="Wageningen"/> ||
 
|-
 
|-
| 1980s || || || “The first trials in the 1980s demonstrated no significant improvement in human milk vitamin D activity with maternal vitamin D intake of 500–1,000 IU/day vitamin D2” <ref name="Holimicf"/>
+
| 1990 || {{w|Cancer}} ([[w:prostate cancer|prostate]])  || Research || Researchers note that the major risk factors for prostate cancer, older age, Black race, and residence at northern latitudes, are all associated with a decreased synthesis of vitamin D.<ref name="Holimicf"/> ||
 
|-
 
|-
| 1990 || || || “In 1990, most endocrine textbooks were emphatic that, with the exception of rare disorders like sarcoidosis, the kidney was the sole organ to hydroxylate the vitamin D prohormone into the active hormone” <ref name="Holimicf"/>
+
| 1990 || {{w|Psoriasis}} || Product launch || Vitamin D derivative {{w|calcipotriol}} is first introduced as ointment for the treatment of psoriasis in Denmark. It is a synthetic [[w:derivative (chemistry)|derivative]] of {{w|calcitriol}}.<ref name="Tarutani">{{cite journal |last1=Tarutani |first1=M |title=[Vitamin D3 for external application--history of development and clinical application]. |journal=Clinical calcium |date=October 2004 |volume=14 |issue=10 |pages=124-8 |pmid=15577144}}</ref> || {{w|Denmark}}
 
|-
 
|-
| 1990 || {{w|Cancer}} ([[w:prostate cancer|prostate]])  || || “In 1990, we noted that the major risk factors for prostate cancer, older age, Black race, and residence at northern latitudes, are all associated with a decreased synthesis of vitamin D” <ref name="Holimicf"/>
+
| 1992 || || Research || A review from M. J. McKenna summarizing the knowledge from 1971–1990 on worldwide vitamin D status, concludes that oral vitamin D intake is lower in Western and Central Europe (2–3 μg/day) than in both North America (5.5–7 μg/day) and Scandinavia (4–6 μg/day) due to a higher ingestion of vitamin D supplementation in Scandinavia and a higher intake of natural sources of vitamin D, such as fatty fish. Plasma 25(OH)D varies with season in both young adults and elderly and is lower during the winter and throughout the year in Central Europe (∼ 18 nmol/l) than in both North America (∼ 58 nmol/l) and Scandinavia (∼ 37 nmol/l). McKenna also concludes that hypovitaminosis D and related skeletal abnormalities are most common in elderly residents in Europe, but are reported in all elderly populations.<ref>{{cite journal |last1=McKenna |first1=Malachi J. |title=Differences in vitamin D status between countries in young adults and the elderly |journal=The American Journal of Medicine |date=July 1992 |volume=93 |issue=1 |pages=69–77 |doi=10.1016/0002-9343(92)90682-2}}</ref> ||
 
|-
 
|-
| 1990 || || || “In a European context van der Wielen et al. in 1995 (24) measured wintertime plasma 25(OH)D in 824 elderly people from 11 European countries. He concluded that freeliving elderly Europeans, regardless of geographical location, were at substantial risk of inadequate vitamin D status during winter. Surprisingly the lowest mean 25(OH)D concentrations were seen in Southern Europe” <ref name="Holimicf"/>
+
| 1992 || {{w|Cancer}} ({{w|prostate cancer|prostate}}) || Research || Geographic analyses show that U.S. county-wide mortality rates for prostate cancer among Caucasian men are inversely correlated with the availability of ultraviolet radiation, the major source of vitamin D.<ref>{{cite journal |last1=Hanchette |first1=Carol L. |last2=Schwartz |first2=Gary G. |title=Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation |journal=Cancer |date=1992 |volume=70 |issue=12 |pages=2861–2869 |doi=10.1002/1097-0142(19921215)70:12<2861::aid-cncr2820701224>3.0.co;2-g}}</ref><ref>{{cite journal |last1=Schwartz |first1=Gary G. |last2=Hanchette |first2=Carol L. |title=UV, latitude, and spatial trends in prostate cancer mortality: All sunlight is not the same (United States) |journal=Cancer Causes & Control |date=October 2006 |volume=17 |issue=8 |pages=1091–1101 |doi=10.1007/s10552-006-0050-6}}</ref> || {{w|United States}}
 
|-
 
|-
| 1990 || || || Calcipotriol ointment is introduced for the treatment of psoriasis in Denmark.<ref name="Tarutani">{{cite journal |last1=Tarutani |first1=M |title=[Vitamin D3 for external application--history of development and clinical application]. |journal=Clinical calcium |date=October 2004 |volume=14 |issue=10 |pages=124-8 |doi=CliCa041015941598 |pmid=15577144}}</ref> || {{w|Denmark}}
+
| 1993 || {{w|Psoriasis}} || Product launch || {{w|Tacalcitol}} ointment is first approved in Japan.<ref name="Tarutani"/> Tacalcitol (1,24-dihydroxyvitamin D<sub>3</sub>) is a synthetic [[w:vitamin D3|vitamin D<sub>3</sub>]] analog.<ref name="pmid9257082">{{cite journal | vauthors = Peters DC, Balfour JA | title = Tacalcitol | journal = Drugs | volume = 54 | issue = 2 | pages = 265–71; discussion 272 | date = August 1997 | pmid = 9257082 | doi = 10.2165/00003495-199754020-00005 }}</ref> It is prescribed for the treatment of {{w|psoriasis}}.<ref>{{cite journal |last1=Lecha |first1=M |last2=Mirada |first2=A |last3=Lopez |first3=S |last4=Artes |first4=M |title=ORIGINAL ARTICLE. Tacalcitol in the treatment of psoriasis vulgaris: the Spanish experience. |journal=Journal of the European Academy of Dermatology and Venereology |date=July 2005 |volume=19 |issue=4 |pages=414–417 |doi=10.1111/j.1468-3083.2005.01099.x}}</ref> || {{w|Japan}}  
 
|-
 
|-
| 1991 || || || {{w|Calcipotriol}} is first approved for medical use.<ref name="sad"/>  
+
| 1994–1999 || Muscle function, bone, and fracture risk || Research || A study conducted in this period in {{w|Montreal}} of blood samples from 256 elderly (aged 65–94 years) apparently healthy, community-dwelling men and women, shows a very surprising 32% of women and 51% of men with 25(OH)D levels below 20 nmol/l<ref>{{cite journal |last1=Vecino-Vecino |first1=Concepción |last2=Gratton |first2=Miren |last3=Kremer |first3=Richard |last4=Rodriguez-Mañas |first4=Leocadio |last5=Duque |first5=Gustavo |title=Seasonal Variance in Serum Levels of Vitamin D Determines a Compensatory Response by Parathyroid Hormone: Study in an Ambulatory Elderly Population in Quebec |journal=Gerontology |date=2006 |volume=52 |issue=1 |pages=33–39 |doi=10.1159/000089823}}</ref>. This level of deficiency is likely to have an adverse effect on muscle function, bone, and fracture risk.<ref name="Holimicf"/> || {{w|Canada}}
 
|-
 
|-
| 1992 || || || “In my ecologic study, I used both July 1992 UVB from the Total Ozone Mapping Spectrometer (65) and latitude, an index of wintertime UVB and vitamin D” <ref name="Holimicf"/>
+
| 1995 || || Research || Dutch research team led by R. P. van der Wielen measure wintertime plasma 25(OH)D ({{w|calcifediol}}) in 824 elderly people from 11 European countries. The team concludes that freeliving elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter. Unexpectedly, the lowest mean 25(OH)D concentrations are seen in Southern Europe.<ref>{{cite journal |last1=van der Wielen |first1=R.P.J. |last2=de Groot |first2=L.C.P.G.M. |last3=van Staveren |first3=W.A. |last4=Löwik |first4=M.R.H. |last5=van den Berg |first5=H. |last6=Haller |first6=J. |last7=Moreiras |first7=O. |title=Serum vitamin D concentrations among elderly people in Europe |journal=The Lancet |date=July 1995 |volume=346 |issue=8969 |pages=207–210 |doi=10.1016/s0140-6736(95)91266-5}}</ref> || {{w|Europe}}
 
|-
 
|-
| 1992 || || || "In a review from 1992 McKenna (23) summarized the present knowledge from 1971–1990 on worldwide vitamin D status. He concluded that oral vitamin D intake was lower in Western and Central Europe (2–3 μg/day) than in both North America (5.5–7 μg/day) and Scandinavia (4–6 μg/day) due to a higher ingestion of vitamin D supplementation in Scandinavia and a higher intake of natural sources of vitamin D, such as fatty fish. Plasma 25(OH)D varied with season in both young adults and elderly and was lower during the winter and throughout the year in Central Europe (∼ 18 nmol/l) than in both North America (∼ 58 nmol/l) and Scandinavia (∼ 37 nmol/l). He also concluded that hypovitaminosis D and related skeletal abnormalities were most com�mon in elderly residents in Europe, but were reported in all elderly populations."<ref name="Holimicf"/>
+
| 1997 || || Research || As the result of 25 years of research, the cytochrome P450, CYP27B1, representing the 1α-Hydroxylase enzyme is finally cloned from a rat renal cDNA library by St Arnaud’s group in Montreal.<ref>{{cite journal |last1=St-Arnaud |first1=René |last2=Messerlian |first2=Serge |last3=Moir |first3=Janet M. |last4=Omdahl |first4=John L. |last5=Glorieux |first5=Francis H. |title=The 25-Hydroxyvitamin D 1-Alpha-Hydroxylase Gene Maps to the Pseudovitamin D-Deficiency Rickets (PDDR) Disease Locus |journal=Journal of Bone and Mineral Research |date=1 October 1997 |volume=12 |issue=10 |pages=1552–1559 |doi=10.1359/jbmr.1997.12.10.1552}}</ref> 1α-Hydroxylase is the key enzyme in vitamin D metabolism.<ref>{{cite journal |last1=Brenza |first1=H. L. |last2=Kimmel-Jehan |first2=C. |last3=Jehan |first3=F. |last4=Shinki |first4=T. |last5=Wakino |first5=S. |last6=Anazawa |first6=H. |last7=Suda |first7=T. |last8=DeLuca |first8=H. F. |title=Parathyroid hormone activation of the 25-hydroxyvitamin D3-1 -hydroxylase gene promoter |journal=Proceedings of the National Academy of Sciences |date=17 February 1998 |volume=95 |issue=4 |pages=1387–1391 |doi=10.1073/pnas.95.4.1387}}</ref> || {{w|Canada}}
 
|-
 
|-
| 1992 || || || “In 1992, the first population-based study of the vitamin D status in Saudi Arabia was published” <ref name="Holimicf"/>
+
| 1997 || || Research || [[w:Vitamin D5|Vitamin D<sub>5</sub>]] is first synthesized by researchers at the Department of Chemistry at the {{w|University of Chicago}}.<ref>{{cite journal |last1=Moriarty |first1=Robert M. |last2=Albinescu |first2=Dragos |title=Synthesis of 1α-Hydroxyvitamin D 5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation |journal=The Journal of Organic Chemistry |date=September 2005 |volume=70 |issue=19 |pages=7624–7628 |doi=10.1021/jo050853f}}</ref> ||
 
|-
 
|-
| 1992 || || || “We proposed that vitamin D maintained the normal phenotype of prostatic cells and that vitamin D deficiency promoted the development of clinical prostate cancer from its preclinical precursors (14). This idea was supported by geographic analyses published in 1992, in which we showed that U.S. county-wide mortality rates for prostate cancer among Caucasian men were inversely correlated with the availability of ultraviolet radiation, the major source of vitamin D” <ref name="Holimicf"/>
+
| 1997 || || Recommendation || The American Academy of Pediatrics and the Canadian Pediatric Association both recommend 400 IU/day of vitamin D, which is twice what the Institute of Medicine (IOM) of the US National Academy of Sciences recommend in the same year.<ref name="Holimicf"/> || {{w|United States}}
 
|-
 
|-
| 1993 || || || “The association was stronger in women aged 60 years and older, suggesting that vitamin D may be more important for postmenopausal breast cancer. The other prospective study of 25(OH)D level and breast cancer risk was based on the PLCO study (65). In this cohort, 1,005 incident cases of breast cancer were frequency matched with 1,005 controls, over follow-up from 1993 to 2005” <ref name="Holimicf"/>
+
| 1997 || || Recommendation || The dietary reference intake panel for calcium, phosphorus, magnesium, vitamin D and fluoride is first established to provide intake recommendations for Americans and Canadians.<ref>{{cite journal |title=Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride |date=17 September 1997 |doi=10.17226/5776}}</ref><ref name="Wageningen"/> || {{w|United States}}, {{w|Canada}}
 
|-
 
|-
| 1993 || || || Tacalcitol ointment is first approved in Japan.<ref name="Tarutani"/> || {{w|Japan}}  
+
| 1997 || || Recommendation  || The U.S. {{w|Institute of Medicine}} (IOM) designates 2,000 IU/day as the TUIL (tolerable upper intake level) of vitamin D intake.<ref name="Holimicf"/> || {{w|United States}}
 
|-
 
|-
| 1994 || || || “The ambulant or institutionalized elderly are considered to be a population at very high risk for vitamin D deficiency. In Montreal, Quebec (45◦N latitude), a study of blood samples, taken between 1994 and 1999, from 256 elderly (aged 65–94 years) apparently healthy, community-dwelling men and women, showed a very surprising 32% of women and 51% of men with 25(OH)D levels below 20 nmol/l (18)” <ref name="Holimicf"/>
+
| 1997 || || Research || Researchers manage to clone the human {{w|25-Hydroxyvitamin D 1-alpha-hydroxylase}}, a secosteroid hormone which plays a crucial role in normal bone growth, calcium metabolism, and tissue differentiation.<ref>{{cite journal |last1=Fu |first1=Glenn K. |last2=Lin |first2=Dong |last3=Zhang |first3=Martin Y. H. |last4=Bikle |first4=Daniel D. |last5=Shackleton |first5=Cedric H. L. |last6=Miller |first6=Walter L. |last7=Portale |first7=Anthony A. |title=Cloning of Human 25-Hydroxyvitamin D-1α-Hydroxylase and Mutations Causing Vitamin D-Dependent Rickets Type 1 |journal=Molecular Endocrinology |date=December 1997 |volume=11 |issue=13 |pages=1961–1970 |doi=10.1210/mend.11.13.0035}}</ref> || {{w|United States}}
 
|-
 
|-
| 1995 || || || "In a European context van der Wielen et al. in 1995 (24) measured wintertime plasma 25(OH)D in 824 elderly people from 11 European countries. He concluded that free�living elderly Europeans, regardless of geographical location, were at substantial risk of inadequate vitamin D status during winter. Surprisingly the lowest mean 25(OH)D concentrations were seen in Southern Europe. This could largely be explained by atti�tudes toward sunlight exposure when users of vitamin D supplements and sunbeds were excluded."<ref name="Holimicf"/>
+
| 1997 || || Research || The Norwegian National Dietary Survey shows that the vitamin D intake is 13% larger in north than in south Norway. This suggests that there is no significant north–south gradient in the level of vitamin D metabolites in serum in that country.<ref name="Holimicf"/> || {{w|Norway}}
 
|-
 
|-
| 1997 || || || “In 1997, as the result of a tremendous amount of attention over 25 years of research, the cytochrome P450, CYP27B1, representing the 1α-hydroxylase enzyme was finally cloned from a rat renal cDNA library by St Arnaud’s group in Montreal (16)” <ref name="Holimicf"/>
+
| 1997 || || Recommendation || The American Academy of Pediatrics (AAP) Committee on Nutrition recommends a dose of vitamin D 400 IU daily as the standard of care for children.<ref name="Holimicf"/> || {{w|United States}}
 
|-
 
|-
| 1997 || || || [[w:Vitamin D5|Vitamin D<sub>5</sub>]] is first synthesized by researchers at the Department of Chemistry at the {{w|University of Chicago}}.<ref>{{cite journal |last1=Moriarty |first1=Robert M. |last2=Albinescu |first2=Dragos |title=Synthesis of 1α-Hydroxyvitamin D 5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation |journal=The Journal of Organic Chemistry |date=September 2005 |volume=70 |issue=19 |pages=7624–7628 |doi=10.1021/jo050853f}}</ref>
+
| 1998 || {{w|Kidney disease}} ({{w|hyperparathyroidism}})|| Drug launch || {{w|Paricalcitol}} (marketed under the trade name Zemplar) is introduced by {{w|Abbott Laboratories}}.<ref>{{cite web |title=Paricalcitol |url=https://go.drugbank.com/drugs/DB00910 |website=go.drugbank.com |access-date=21 September 2021}}</ref> || {{w|United States}}
 
|-
 
|-
| 1997 || || Recommendation || The American Academy of Pediatrics and the Canadian Pediatric Association both recommend 400 IU/day of vitamin D, which is twice what the Institute of Medicine (IOM) of the US National Academy of Sciences recommend in the same year.<ref name="Holimicf"/>
+
| 1998 || {{w|Cancer}} ({{w|prostate cancer|prostate}}) || Research || It is demonstrated that normal human prostate cells possess 25-hydroxyvitamin D3–1α-hydroxylase (1α(OH)ase) and indeed synthesize 1,25(OH)2D from 25(OH)D.<ref>{{cite journal |last1=Schwartz |first1=GG |last2=Whitlatch |first2=LW |last3=Chen |first3=TC |last4=Lokeshwar |first4=BL |last5=Holick |first5=MF |title=Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. |journal=Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology |date=May 1998 |volume=7 |issue=5 |pages=391-5 |pmid=9610788}}</ref> || {{w|United States}} ({{w|University of Miami School of Medicine}})
 
|-
 
|-
| 1997 || || || The dietary reference intake panel for calcium, phosphorus, magnesium, vitamin D and fluoride is first established to provide intake recommendations for Americans and Canadians.<ref>{{cite journal |title=Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride |date=17 September 1997 |doi=10.17226/5776}}</ref><ref name="Wageningen"/> || {{w|United States}}, {{w|Canada}}
+
| 1999 || {{w|Asthma}}, {{w|allergy}} || Research || Wjst and Dold, in trying to explain the rise in asthma and allergy rates, propose their hypothesis that the introduction of vitamin D in fortified foods and in multivitamin preparations in many westernized countries is related to the asthma and allergy epidemic in these countries.<ref name="Litonjua"/> They propose that vitamin D supplementation might be the cause of global increases in asthma and allergies.<ref name="Hewison">{{cite book |last1=Hewison |first1=Martin |last2=Bouillon |first2=Roger |last3=Giovannucci |first3=Edward |last4=Goltzman |first4=David |title=Vitamin D: Volume 2: Health, Disease and Therapeutics |date=14 December 2017 |publisher=Academic Press |isbn=978-0-12-809964-3 |url=https://books.google.com.ar/books?id=sBZHDgAAQBAJ&pg=PA1096&lpg=PA1096&dq=1999+Wjst+and+Dold+propose+that+vitamin+D+supplementation+might+be+the+cause+of+global+increases+in+asthma+and+allergies&source=bl&ots=vBDqaHlLYS&sig=ACfU3U3xc3Wc6xBd4CWFYs2EvTXelwZzew&hl=en&sa=X&ved=2ahUKEwjhw_i1s_ryAhXXppUCHcxVBwQQ6AF6BAgCEAM#v=onepage&q=1999%20Wjst%20and%20Dold%20propose%20that%20vitamin%20D%20supplementation%20might%20be%20the%20cause%20of%20global%20increases%20in%20asthma%20and%20allergies&f=false |language=en}}</ref> ||
 
|-
 
|-
| 1997 || || || “The safety of higher doses of vitamin D supplementation has been discussed in Chapter 31. The National Academy of Sciences Institute of Medicine (IOM) had designated 2,000 IU/day as the TUIL (tolerable upper intake level) of vitamin D intake in 1997 but did not relate that dose to serum 25(OH)D concentrations” <ref name="Holimicf"/>
+
| 1999 || || Literature || {{w|Michael F. Holick}} publishes ''Vitamin D: Molecular Biology, Physiology, and Clinical Applications''.<ref>{{cite book |last1=Holick |first1=Michael F. |title=Vitamin D: Molecular Biology, Physiology, and Clinical Applications |date=1999 |publisher=Humana Press |isbn=978-0-89603-467-9 |url=https://books.google.com.ar/books/about/Vitamin_D.html?id=bQNrAAAAMAAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> || {{w|United States}}
 
|-
 
|-
| 1997 || || || “With the cloning of the 25(OH)D 1α hydroxylase (CYP27B1) in 1997 by four groups (15–18) and the subsequent development of antibodies to CYP27B1 (19), CYP27B1 expression was readily demonstrated in a wide variety of tissues. In that the vitamin D receptor (VDR) is also found in a wide variety of tissues, the question of the physiologic significance of these observations must be addressed” <ref name="Holimicf"/>
+
| 2000 || {{w|Cancer}} ({{w|prostate cancer|prostate}}) || Research || Researchers show that 25(OH)D ({{w|calcifediol}}) inhibits the proliferation of prostate cells that possess 1α-OHase.<ref>{{cite journal |last1=Barreto |first1=AM |last2=Schwartz |first2=GG |last3=Woodruff |first3=R |last4=Cramer |first4=SD |title=25-Hydroxyvitamin D3, the prohormone of 1,25-dihydroxyvitamin D3, inhibits the proliferation of primary prostatic epithelial cells. |journal=Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology |date=March 2000 |volume=9 |issue=3 |pages=265-70 |pmid=10750664}}</ref> || {{w|United States}} ({{w|Wake Forest School of Medicine}}, {{w|Winston-Salem, North Carolina}})
 
|-
 
|-
| 1997 || || || The Norwegian National Dietary Survey shows that the vitamin D intake is 13% larger in north than in south Norway. This suggests that there is no significant north–south gradient in the level of vitamin D metabolites in serum in that country.<ref name="Holimicf"/> || {{w|Norway}}
+
| 2001 || {{w|Kidney disease}} (secondary {{w|hyperparathyroidism}}) || Drug launch || {{w|Doxercalciferol}} (marketed under the trade name Hectorol) is first introduced in {{w|Canada}} by Sanofi Genzyme. It is a synthetic vitamin D2 analog used to treat secondary hyperparathyroidism in patients with chronic kidney disease with or without therapy of dialysis.<ref>{{cite web |title=Doxercalciferol |url=https://go.drugbank.com/drugs/DB06410 |website=go.drugbank.com |access-date=21 September 2021}}</ref> || {{w|Canada}}
 
|-
 
|-
| 1997 || || || “As part of the 1997 DRIs, a daily tolerable upper intake level (UL) for vitamin D of 50 μg (2,000 IU) (18) was established for persons aged 1 year and older in order to discourage potentially dangerous self-medication” <ref name="Holimicf"/>
+
| 2003 || || Recommendation || In response to the vitamin D adequate intake recommendations made by the Institute of Medicine in 1997, the Committee on Nutrition of the American Academy of Pediatrics recommends 200 IU/d vitamin D for all infants and children.<ref name="Frank R"/> || {{w|United States}}
 
|-
 
|-
| 1997 || || || “A recent risk assessment for vitamin D used new data (post-1997) to derive a “revised” UL (35). Studies indicated that there was absence of any signs of toxicity when healthy adults were given over 250 μg (10,000 IU) daily” <ref name="Holimicf"/>
+
| 2005 || || Literature || David Feldman, J. Wesley Pike and Francis H. Glorieux publish ''Vitamin D'', which includes over 100 chapters covering from chemistry and metabolism to mechanisms of action, diagnosis and management, new analogs, and emerging therapies involving vitamin D.<ref>{{cite book |last1=Feldman |first1=David |last2=Pike |first2=J. Wesley |last3=Glorieux |first3=Francis H. |title=Vitamin D |date=25 January 2005 |publisher=Elsevier |isbn=978-0-08-054364-2 |url=https://books.google.com.ar/books/about/Vitamin_D.html?id=5c66r0KrPUMC&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1997 || || || “A number of specialty groups are now recommending higher intakes than the Institute of Medicine AIs recommended in 1997; e.g., Osteoporosis Canada’s 2002 Clinical Practice Guidelines recommend a minimum intake of 20 μg (800 IU) vitamin D daily for individuals over age 50 years” <ref name="Holimicf"/>
+
| 2006 || {{w|Cancer}} (digestive-system) || Research || A study by researchers at Harvard Medical School, analizing 1095 men and documents from 1986 through 2000 of 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer, concludes that low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers.<ref>{{cite journal |last1=Giovannucci |first1=Edward |last2=Liu |first2=Yan |last3=Rimm |first3=Eric B. |last4=Hollis |first4=Bruce W. |last5=Fuchs |first5=Charles S. |last6=Stampfer |first6=Meir J. |last7=Willett |first7=Walter C. |title=Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men |journal=JNCI: Journal of the National Cancer Institute |date=5 April 2006 |volume=98 |issue=7 |pages=451–459 |doi=10.1093/jnci/djj101}}</ref> || {{w|United States}}
 
|-
 
|-
| 1997 || || || The American Academy of Pediatrics (AAP) Committee on Nutrition recommends a dose of vitamin D 400 IU daily as the standard of care for children.<ref name="Holimicf"/> || {{w|United States}}
+
| 2007 || {{w|Cancer}} ([[w:breast cancer|breast]] || Research || Garland et al. publish a breast cancer doseresponse meta-analysis, finding that individuals with the highest blood levels of 25-hydroxyvitamin D has reduced risk of {{w|breast cancer}}.<ref>{{cite journal |last1=Garland |first1=Cedric F. |last2=Gorham |first2=Edward D. |last3=Mohr |first3=Sharif B. |last4=Grant |first4=William B. |last5=Giovannucci |first5=Edward L. |last6=Lipkin |first6=Martin |last7=Newmark |first7=Harold |last8=Holick |first8=Michael F. |last9=Garland |first9=Frank C. |title=Vitamin D and prevention of breast cancer: Pooled analysis |journal=The Journal of Steroid Biochemistry and Molecular Biology |date=March 2007 |volume=103 |issue=3-5 |pages=708–711 |doi=10.1016/j.jsbmb.2006.12.007}}</ref><ref name="Mohrv"/> || {{w|United States}}
 
|-
 
|-
| 1997 || || || Fu et al. clone 25OHD-1-alpha-hydroxylase.<ref name="Hochberg"/>
+
| 2007 || {{w|Anaphylaxis}} || Research || Camargo and colleagues propose that vitamin D status might influence risk of food-induced {{w|anaphylaxis}} (FIA) after observing a strong north–south gradient in epinephrine autoinjector prescription rates in the United States.<ref>{{cite journal |last1=Vassallo |first1=M. F. |last2=Banerji |first2=A. |last3=Rudders |first3=S. A. |last4=Clark |first4=S. |last5=Camargo |first5=C. A. |title=Season of birth and food-induced anaphylaxis in Boston: ALLERGYNet |journal=Allergy |date=November 2010 |volume=65 |issue=11 |pages=1492–1493 |doi=10.1111/j.1398-9995.2010.02384.x}}</ref> || {{w|United States}} ({{w|Boston}})
 
|-
 
|-
| 1998 || {{w|Rickets}} || || “Although there are few good prevalence estimates, in 1998 the incidence of rickets in 0- to 3-year olds attributed to vitamin D deficiency in eastern Turkey was 6.1% based on clinical signs” <ref name="Holimicf"/>
+
| 2007 || {{w|Psoriasis}} || Drug launch || CollaGenex Pharmaceuticals licenses becocalcidiol, a vitamin D analogue for topical treatment of psoriasis and psoriatic disorders.<ref>{{cite web |title=Becocalcidiol |url=https://go.drugbank.com/drugs/DB04891 |website=go.drugbank.com |access-date=21 September 2021}}</ref><ref>{{cite web |title=The Biologics News and Reports Portal |url=https://pipelinereview.com/index.php/2008011417152/Small-Molecules/CollaGenex-Pharmaceuticals-Initiates-Phase-2-Dose-Finding-Study-of-Becocalcidiol-for-the-Treatment-of-Psoriasis.html |website=pipelinereview |access-date=21 September 2021 |language=en-gb}}</ref> || {{w|United States}}
 
|-
 
|-
| 1998 || || || “In 1998, we demonstrated that normal human prostate cells possess 25-hydroxyvitamin D3–1α-hydroxylase (1α(OH)ase) and indeed synthesize 1,25(OH)2D from 25(OH)D (31). Moreover, we and others showed that 25(OH)D inhibits the proliferation of prostate cells that possess 1α-OHase” <ref name="Holimicf"/>
+
| 2008 || {{w|Skin cancer}} || Literature || Jörg Reichrath publishes ''Sunlight, Vitamin D and Skin Cancer'', which provides an overview of positive and negative effects of {{w|ultraviolet}}-exposure, with a focus on Vitamin D and skin cancer.<ref>{{cite book |last1=Reichrath |first1=Jörg |title=Sunlight, Vitamin D and Skin Cancer |date=11 September 2020 |publisher=Springer Nature |isbn=978-3-030-46227-7 |url=https://books.google.com.ar/books/about/Sunlight_Vitamin_D_and_Skin_Cancer.html?id=lqT8DwAAQBAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1999 || || || “The trends evident in Table 2 include higher intakes in men than in women when food sources alone are considered and an increase in vitamin D intake with increasing age when supplements use is common. In a more recent NHANES 1999–2000 study, mean intake from food and mean intake from food and supplements were reported” <ref name="Holimicf"/>
+
| 2008 || || Recommendation || The {{w|American Academy of Pediatrics}} increases the recommended supplementation dose from 200 to 400 IU daily across the pediatric age spectrum.<ref>{{cite journal |last1=Wagner |first1=C. L. |last2=Greer |first2=F. R. |title=Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents |journal=PEDIATRICS |date=1 November 2008 |volume=122 |issue=5 |pages=1142–1152 |doi=10.1542/peds.2008-1862}}</ref> || {{w|United States}}
 
|-
 
|-
| 1999 || || || ", in 1999, Wjst and Dold [ 44 ] , in trying to explain the rise in asthma and allergy rates, proposed their hypothesis that the introduction of vitamin D in forti fi ed foods and in multivitamin preparations in many westernized countries was related to the asthma and allergy epidemic in these countries."<ref name="Litonjua"/>  Wjst and Dold propose that vitamin D supplementation might be the cause of global increases in asthma and allergies.<ref name="Hewison">{{cite book |last1=Hewison |first1=Martin |last2=Bouillon |first2=Roger |last3=Giovannucci |first3=Edward |last4=Goltzman |first4=David |title=Vitamin D: Volume 2: Health, Disease and Therapeutics |date=14 December 2017 |publisher=Academic Press |isbn=978-0-12-809964-3 |url=https://books.google.com.ar/books?id=sBZHDgAAQBAJ&pg=PA1096&lpg=PA1096&dq=1999+Wjst+and+Dold+propose+that+vitamin+D+supplementation+might+be+the+cause+of+global+increases+in+asthma+and+allergies&source=bl&ots=vBDqaHlLYS&sig=ACfU3U3xc3Wc6xBd4CWFYs2EvTXelwZzew&hl=en&sa=X&ved=2ahUKEwjhw_i1s_ryAhXXppUCHcxVBwQQ6AF6BAgCEAM#v=onepage&q=1999%20Wjst%20and%20Dold%20propose%20that%20vitamin%20D%20supplementation%20might%20be%20the%20cause%20of%20global%20increases%20in%20asthma%20and%20allergies&f=false |language=en}}</ref>
+
| 2008 || || Literature || James Dowd and Diane Stafford publish ''The Vitamin D Cure''.<ref>{{cite book |last1=MD |first1=James Dowd |last2=Stafford |first2=Diane |title=The Vitamin D Cure |date=14 January 2008 |publisher=John Wiley & Sons |isbn=978-0-470-13155-8 |url=https://books.google.com.ar/books/about/The_Vitamin_D_Cure.html?id=kkQto717kroC&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1990s || || || ". Historically, measurements of 25(OH)D were performed in research centers using high-pressure liquid chromatography (HPLC) or competitive protein-binding methods (CBP). In the 1990s, validated radioimmunoassay (RIA) and other methods were developed, such as enzyme-linked immunosorbent assay (ELISA) or chemolu�miniescence. The recent clinical availability of liquid chromatography tandem mass spectroscopy (LCMSMS) and HPLC technologies has improved 25(OH)D assay performance, leading to higher agreement between measurements obtained at differ�ent clinical laboratori"<ref name="Holimicf"/>
+
| 2009 || || Literature || Soram Khalsa publishes ''Vitamin D Revolution''.<ref>{{cite book |last1=M.D |first1=Soram Khalsa |title=Vitamin D Revolution |date=1 March 2009 |publisher=Hay House, Inc |isbn=978-1-4019-2911-4 |url=https://books.google.com.ar/books/about/Vitamin_D_Revolution.html?id=5H4zfBJNbyUC&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 1990s || || || “However, there was little progress on the vitamin D/non-calcemic disease paradigm until the 1990s, but in the first years of the twenty-first century interest has skyrocketed” <ref name="Holimicf"/>
+
| 2010 || {{w|Pneumonia}} || Research || A randomized clinical trial finds that vitamin D supplementation reduces the risk of pneumonia in children.<ref name="Wageningen"/> ||
 
|-
 
|-
| 2003 || || || In response to the vitamin D adequate intake recommendations made by the Institute of Medicine in 1997, the Committee on Nutrition of the American Academy of Pediatrics recommends 200 IU/d vitamin D for all infants and children.<ref name="Frank R"/>
+
| 2010 || {{w|Rheumatoid arthritis}} || Research || A study in Italy inversely relates {{w|rheumatoid arthritis}} activity and disability scores with {{w|calcifediol}} concentrations.<ref name="Wageningen"/> || {{w|Italy}}
 
|-
 
|-
| 2007 || || || Garland et al. publish a breast cancer doseresponse meta-analysis, finding that individuals with the highest blood levels of 25-hydroxyvitamin D has reduced risk of {{w|breast cancer}}.<ref>{{cite journal |last1=Garland |first1=Cedric F. |last2=Gorham |first2=Edward D. |last3=Mohr |first3=Sharif B. |last4=Grant |first4=William B. |last5=Giovannucci |first5=Edward L. |last6=Lipkin |first6=Martin |last7=Newmark |first7=Harold |last8=Holick |first8=Michael F. |last9=Garland |first9=Frank C. |title=Vitamin D and prevention of breast cancer: Pooled analysis |journal=The Journal of Steroid Biochemistry and Molecular Biology |date=March 2007 |volume=103 |issue=3-5 |pages=708–711 |doi=10.1016/j.jsbmb.2006.12.007}}</ref><ref name="Mohrv"/> || {{w|United States}}
+
| 2011 (January) || {{w|Osteoporosis}} || Drug launch || {{w|Eldecalcitol}} is approved in {{w|Japan}}, for the treatment for {{w|osteoporosis}}.<ref name=medchem>{{Cite book | vauthors = Bronson J, Dhar M, Ewing W, Lonberg N | veditors = Desai MC | chapter = To Market — 2011: Eldecalcitol (osteoporosis) | title = Annual Reports in Medicinal Chemistry | publisher = Elsevier Inc. | volume = 47 | edition = 1st | location = San Diego | date = 2012 | pages = 529–531 | isbn = 9780123964922 }}</ref>  It is an [[w:structural analog|analog]] of {{w|vitamin D}}.<ref>{{cite journal |last1=Hatakeyama |first1=Susumi |last2=Yoshino |first2=Madoka |last3=Eto |first3=Kohei |last4=Takahashi |first4=Keisuke |last5=Ishihara |first5=Jun |last6=Ono |first6=Yoshiyuki |last7=Saito |first7=Hitoshi |last8=Kubodera |first8=Noboru |title=Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71] |journal=The Journal of Steroid Biochemistry and Molecular Biology |date=July 2010 |volume=121 |issue=1-2 |pages=25–28 |doi=10.1016/j.jsbmb.2010.03.041}}</ref> || {{w|Japan}}
 
|-
 
|-
| 2007 || {{w|Anaphylaxis}} || || Camargo and colleagues propose that vitamin D status might influence risk of food-induced {{w|anaphylaxis}} (FIA) after observing a strong north–south gradient in epinephrine autoinjector prescription rates in the United States.<ref>{{cite journal |last1=Vassallo |first1=M. F. |last2=Banerji |first2=A. |last3=Rudders |first3=S. A. |last4=Clark |first4=S. |last5=Camargo |first5=C. A. |title=Season of birth and food-induced anaphylaxis in Boston: ALLERGYNet |journal=Allergy |date=November 2010 |volume=65 |issue=11 |pages=1492–1493 |doi=10.1111/j.1398-9995.2010.02384.x}}</ref> || {{w|United States}} ({{w|Boston}})
+
| 2012 || || Literature || Ian Wishart publishes ''Vitamin D: Is This the Miracle Vitamin?'', which claims that taking vitamin D reduces up to a 77% the risk of developing cancer.<ref>{{cite book |last1=Wishart |first1=Ian |title=Vitamin D: Is This the Miracle Vitamin? |date=2012 |publisher=Howling at the Moon Publishing |isbn=978-0-9876573-1-2 |url=https://books.google.com.ar/books/about/Vitamin_D.html?id=9QR3MAEACAAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 2008 || || || “In 2003, the AAP recommended supplementation with 200 IU daily across the pediatric age spectrum (93) and in 2008, increased the supplementation dose to 400 IU daily” <ref name="Holimicf"/>
+
| 2016 || || Literature || Ana Claudia Domene publishes ''Multiple Sclerosis and (lots Of) Vitamin D'', which introduces the Coimbra Protocol, a therapeutic approach that relies on high doses of vitamin D with the purpose to boost the immune system.<ref>{{cite book |last1=Domene |first1=Ana Claudia |title=Multiple Sclerosis and (lots Of) Vitamin D: My Eight-Year Treatment with The Coimbra Protocol for Autoimmune Diseases |date=18 February 2016 |publisher=CreateSpace Independent Publishing Platform |isbn=978-1-5191-6531-2 |url=https://books.google.com.ar/books/about/Multiple_Sclerosis_and_lots_Of_Vitamin_D.html?id=RIRVjwEACAAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 2010 || || || A randomized clinical trial finds that vitamin D supplementation reduces the risk of pneumonia in children.<ref name="Wageningen"/>  
+
| 2018 || {{w|Cancer}} ([[w:colorectal cancer|colorectal]]) || Research || A study by an international group of researchers using data from about 12,800 people finds that higher levels of vitamin D in the blood is associated with a lower risk for getting {{w|colorectal cancer}}.10.1093/jnci/djy087<ref>{{cite web |title=Vitamin D Levels Linked to Lower Colorectal Cancer Risk |url=https://www.cancer.org/latest-news/vitamin-d-levels-linked-to-lower-colorectal-cancer-risk.html |website=www.cancer.org |access-date=20 September 2021 |language=en}}</ref> || 
 
|-
 
|-
| 2010 || {{w|Rheumatoid arthritis}} || || "A study in Italy inversely related RA disease activity and disability scores with 25(OH)D concentrations (Rossini, et al., 2010)."<ref name="Wageningen"/> || {{w|Italy}}
+
| 2018 || || Literature || Emilia Pauline Liao publishes ''Extraskeletal Effects of Vitamin D: A Clinical Guide'', which provides an examination of extraskeletal effects of vitamin D and the associations between vitamin D deficiency and various disease states.<ref>{{cite book |last1=Liao |first1=Emilia Pauline |title=Extraskeletal Effects of Vitamin D: A Clinical Guide |date=23 April 2018 |publisher=Humana Press |isbn=978-3-319-73742-3 |url=https://books.google.com.ar/books/about/Extraskeletal_Effects_of_Vitamin_D.html?id=SYlXDwAAQBAJ&source=kp_book_description&redir_esc=y |language=en}}</ref> ||
 
|-
 
|-
| 2011 (January) || {{w|Osteoporosis}} || || {{w|Eldecalcitol}} is approved in {{w|Japan}}, where it is used for the treatment for {{w|osteoporosis}}.<ref name=medchem>{{Cite book | vauthors = Bronson J, Dhar M, Ewing W, Lonberg N | veditors = Desai MC | chapter = To Market — 2011: Eldecalcitol (osteoporosis) | title = Annual Reports in Medicinal Chemistry | publisher = Elsevier Inc. | volume = 47 | edition = 1st | location = San Diego | date = 2012 | pages = 529–531 | isbn = 9780123964922 }}</ref>
+
| 2020 (July) || {{w|COVID-19}} || Literature || David C. Anderson and David S. Grimes publish ''Vitamin D Deficiency and Covid-19: Its Central Role in a World Pandemic'', which emphasizes the immunity provided by adequate levels of Vitamin D against the invasion by all new viruses.<ref>{{cite book |title=Vitamin D Deficiency and Covid-19: Its Central Role in a World Pandemic |isbn=0956213278}}</ref> ||
 
|-
 
|-
| 2021 (January 14) || || Research || A randomized controlled trial of {{w|vitamin D}} supplements led by {{w|QIMR Berghofer Medical Research Institute}} in {{w|Australia}} finds they do not protect most people from developing colds, influenza and other acute respiratory infections.<ref>{{cite web |title=Clinical trial finds vitamin D does not ward off colds and flu |url=https://medicalxpress.com/news/2021-01-clinical-trial-vitamin-d-ward.html |website=medicalxpress.com |access-date=19 March 2021 |language=en}}</ref>
+
| 2021 (January 14) || {{w|Common cold}}, {{w|influenza}}, {{w|influenza-like illness}} || Research || A randomized controlled trial of {{w|vitamin D}} supplements led by {{w|QIMR Berghofer Medical Research Institute}} in {{w|Australia}} finds they do not protect most people from developing colds, influenza and other acute respiratory infections.<ref>{{cite web |title=Clinical trial finds vitamin D does not ward off colds and flu |url=https://medicalxpress.com/news/2021-01-clinical-trial-vitamin-d-ward.html |website=medicalxpress.com |access-date=19 March 2021 |language=en}}</ref> || {{w|Australia}}
 
|-
 
|-
 
|}
 
|}
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===What the timeline is still missing===
 
===What the timeline is still missing===
  
 +
* Helpful / harmful / no effect column?
 +
* [https://vitamindwiki.com/VitaminDWiki Vitamin D Wiki] (both the launch of the wiki itself, and some content in it)
 +
* Vitamin D cofactors: relation with Vitamin A, Vitamin K, and magnesium
 +
* [https://slatestarcodex.com/2014/01/25/beware-mass-produced-medical-recommendations/ Beware Mass-Produced Medical Recommendations]
 +
* [https://go.drugbank.com/categories/DBCAT002152]
 +
* [https://www.ehealthme.com/condition/vitamin-d-deficiency/]
 
* {{w|Category:Vitamin D}}
 
* {{w|Category:Vitamin D}}
 
* {{w|Vitamin D}}
 
* {{w|Vitamin D}}
 
* {{w|Vitamin D deficiency}}
 
* {{w|Vitamin D deficiency}}
 +
** Also how vegan diets are at higher risk of vitamin D deficiency without supplementation
 
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529528/] <ref name="Evolutionary Pe"/>
 
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529528/] <ref name="Evolutionary Pe"/>
  
Line 522: Line 521:
  
 
* [[Timeline of malnutrition]]
 
* [[Timeline of malnutrition]]
 +
* [[Timeline of nutritional supplements]]
  
 
==External links==
 
==External links==

Latest revision as of 15:44, 7 May 2023

This is a timeline of vitamin D, attempting to describe significant and illustrative events in the history of vitamin D.

Sample questions

The following are some interesting questions that can be answered by reading this timeline:

  • What are some important events preceeding the discovery of vitamin D?
    • Sort the full timeline by "Event type" and look for the group of rows with value "Prelude".
    • You will see some important events related to the history of vitamin D, like the first description of rickets, and early treatments involving vitamin D, such as cod liver oil.
  • What are some health conditions related to vitamin D named in this timeline?
    • Sort the full timeline by "Related health condition (when applicable)".
    • You will see a range of conditions, often rickets, but also cancer and kidney disease, among others.
  • What are some significant or illustrative studies being conducted on Vitamin D?
    • Sort the full timeline by "Event type" and look for the group of rows with value "Research".
    • You will see a variety of studies of different types, from cohort studies indicating the effect of vitamin D in subjects, to laboratory studies such as molecular cloning.
  • What are some Vitamin D recommended intakes published by competent institutions?
    • Sort the full timeline by "Event type" and look for the group of rows with value "Recommendation".
    • Check table of recommendations for vitamin D for adults in Canada and United States.
  • What are some vitamin D-related drugs having been launched to the market?
    • Sort the full timeline by "Event type" and look for the group of rows with value "Drug launch".
    • You will see a list of marketed analogs of vitamin D.
  • What are some illustrative books specializing in vitamin D?
    • Sort the full timeline by "Event type" and look for the group of rows with value "Literature".
    • You will see a number of publications, some by notable authors such as Michael F. Holick.

Big picture

Time period Development summary More details
Before 1770 Pre–modern history of vitamin D Rickets, a condition caused by vitamin D deficiency, is already described as early as in the 2nd century AD. The disease is first identified as a rare disorder in the 1600s, when most people live rural lives with abundant sun exposure.
1770–1920 Cod liver oil as major vitamin D source Cod liver oil, rich in vitamin D, is first advocated for the treatment of a disease (tuberculosis). In the late 1700s rickets becomes rampant in Europe as people begin to stay indoors and live in large, polluted cities, with reduced exposure to sunlight. Cod liver oil is first prescribed in 1824 for the treatment of rickets. The modern history of vitamin D begins in the mid-19th century, when it is noticed that city children are more likely to have rickets than rural children.[1]
1920 onwards Post–vitamin D discovery era Vitamin D is discovered during research into the causes and treatment of rickets.[2][3] The essential role of vitamin D in mineral homeostasis and skeletal health is recognized since the 1930s, when vitamin D fortification of milk eradicates rickets.[4] vitamin D2 starts being used as a dietary supplement in lieu of vitamin D3.[4] In the 1940s, the United States and Canada start setting dietary intake recommendations for nutrients. In the 1960s, it is clearly demonstrated the vitamin D is a pro-hormone, and that it needs to undergo several stepwise conversions in the body, firstly in the skin, then in the circulating plasma, the liver, and finally in the kidney.[5]

Numerical and visual data

The table below shows recommendations for vitamin D for adults in Canada and United States from 1968 to 1997.[6]

Country and date Age groupings (years) Recommended value (μg (IU))
United States
1968 18-22 10 (400)
22-35 10 (400)
35-55 None given
55-75+ None given
1974 19-22 10 (400)
23-50 10 (400)
51+ 10 (400)
1980 19-22 7.5 (300)
23-50 5 (200)
51+ 5 (200)
1989 19-24 10 (400)
25-50 5(200)
51+ 5(200)
Canada
1964 "Adult" None given
1975 19-35 2.5 (100)
36-50 2.5 (100)
51+ 2.5 (100)
1983 19-24 2.5 (100)
25-49 2.5 (100)
50-74 2.5 (100)
75+ 2.5 (100)
1990 19-24 2.5 (100)
25-49 2.5 (100)
50-74 5 (200)
75+ 5 (200)
Canada and United States (DRI)
1997 19-30 5 (200)
31-50 5 (200)
51-70 10 (400)
>70 15 (600)


Trend of “Vitamin d deficiency” reports.[7]

Year Number of reports submitted
1997
1998 5
1999 8
2000 22
2001 8
2002 9
2003 18
2004 31
2005 26
2006 33
2007 66
2008 187
2009 359
2010 621
2011 1,223
2012 2,116
2013 1,180
2014 1,480
2015 1,712
2016 1,894
2017 2,395
2018 2,742
2019 2,569
2020 2,868
Vitamin D grfok.png

Google Scholar

The following table summarizes per-year mentions on Google Scholar as of September 19, 2021.

Year "vitamin D"
1920 16
1930 502
1940 723
1950 932
1960 950
1970 1,780
1980 3,350
1990 4,350
2000 9,600
2010 30,000
2020 45,300
Vitamin D gsh.png

Google Trends

The chart below shows Google Trends data for Vitamin D, from January 2004 to September 2021, when the screenshot was taken. Interest is also ranked by country and displayed on world map.[8]

Vitamin D gt.png

Google Ngram Viewer

The comparative chart below shows Google Ngram Viewer data for vitamin D, vitamin A, vitamin B and vitamin C, from 1900 to 2019.[9]

Vitamin D ngram.png

Wikipedia Views

The chart below shows pageviews of the English Wikipedia article Vitamin D, from July 2015 to August 2021.[10]

Vitamin D wv.png

Full timeline

Year Related health condition (when applicable) Event type Details Location/researcher affiliation
2nd century AD Rickets Prelude Rickets, the bone disease caused by vitamin D deficiency, is described by Soranus of Ephesus’s in Roman children.[11]
1650 Rickets Prelude Rickets is described in detail by British physician Francis Glisson.[12] United Kingdom
1770 Tuberculosis Prelude (medical development) Cod liver oil, rich in vitamin D, is first advocated for the treatment of tuberculosis.[13] Derived from liver of cod fish (Gadidae), today it is a dietary supplement.
1822 Rickets Prelude (research) Polish physician Jędrzej Śniadecki observes that lack of sunlight exposure is likely a cause of rickets.[14] Poland
1824 Rickets Prelude (medical development) Although having been used medicinally for a long time, cod liver oil (which has vitamin D) is first prescribed by D. Scheutte for the treatment of rickets.[12]
1849 Tuberculosis Prelude (research) English physician Charles Theodore Williams reports the results of administering fish liver oil (vitamin D) to 234 patients with tuberculosis. He notes an important improvement in a few days and concludes that ”the pure fresh oil from the liver of the cod is more beneficial in the treatment of pulmonary consumption than any agent, medicinal, dietetic, or regiminal, that has yet been employed“.[15] United Kingdom
1849 Tuberculosis Prelude (medical development) Cod liver oil is recognized in Europe as beneficial in the treatment of tuberculosis.[4] Europe
1890 Rickets Prelude (research) British medical missionary and epidemiologist Theodore Palm notes through his travels that children living in equatorial countries do not develop rickets.[1]
1903 Tuberculosis Prelude (research) Faroese physician Niels Ryberg Finsen is awarded the Nobel Prize in Physiology or Medicine for his discovery that shortwave ultraviolet light is effective in the treatment of cutaneous tuberculosis.[2]
1906 Rickets Prelude (research) English biochemist Frederick Gowland Hopkins postulates the existence of essential dietary factors necessary for the prevention of diseases such as scurvy or rickets.[12][16] United Kingdom
1912 Prelude (research) Frederick Gowland Hopkins describes the vitamins.[11] United Kingdom
1914 Rickets Prelude (research) McCollum and co-workers conduct a series of experiments that would lead to the discovery of vitamin D. The team manages to isolate a substance from butterfat, necessary for prevention of xerophthalmia in rats, and name it “fat-soluble factor A”. They subsequently report that heated oxidized cod-liver oil could not prevent xerophthalmia but could cure rickets in rats, and conclude that “fatsoluble factor A” consists of two entities, one which could prevent xerophthalmia (subsequently called vitamin A) and one which cured rickets (subsequently called vitamin D, as the terms vitamin B and vitamin C have already been coined).[2][17] United States (Wisconsin Agricultural Experiment Station, University of Wisconsin–Madison)
1919 Prelude (research) British biochemist Edward Mellanby observes that dogs who were fed a diet of mostly oatmeal and kept indoors away from the sun could be cured of the disease by providing cod liver oil.[18] United Kingdom
1921 Rickets Prelude (research) Hess and Unger observe that “seasonal incidence of rickets is due to seasonal variations of sunlight.”[12]
1922 Rickets Research American biochemist Elmer McCollum at Johns Hopkins University discovers Vitamin D from cod liver oil as a dietary substance that could prevent rickets.[19] United States
1922 Rickets Research Sniadecki notices that children living on farms in Poland do not develop rickets, in contrast to children living in the city of Warsaw, who has high incidence of the disease at the time. He hypothesizes that increased exposure to sunlight in the children living in rural areas prevents them from developing rickets.[1] Poland
1922 Rickets Research British microbiologist Hariette Chick and her co-workers, working with malnourished children in a clinic in Vienna, show that rickets prevalent in the children could be cured by whole milk or cod-liver oil.[12] Austria
1923 Rickets Research Harry Goldblatt and Katharine Marjorie Soames show the conversion of a precursor to vitamin D in the skin under the effect of ultraviolet light. They also observe that livers of irradiated rats are curative when fed to rachitic rats.[20][11]
1926 Research Rosenheim and Webster, at a meeting of the Biochemical Society in London, announce that “the precursor of vitamin D is not cholesterol itself, but a substance which is associated with and follows ‘chemically pure' cholesterol in all its stages of purification by the usual methods (saponification and recrystallization).”[12] United Kingdom
1928 Tooth decay Research An experiment by Mellanby and Pattison with children finds that oral vitamin D intake reduces the risk of dental caries.[19]
1930 Drug launch Vitamin D prodrug dihydrotachysterol is developed as a method of stabilizing the triene structure of one of the photoisomers of vitamin D. This represents the oldest vitamin D analog.[4]
1931 Research Vitamin D2 is purified and crystallized simultaneously by researchers in London and the Netherlands.[2][12] United Kingdom, Netherlands
1932 Research The structure of vitamin D is identified when Askew et al. manage to isolate vitamin D2 from a mixture of ergosterol (a compound found in fungi).[18]
1933 Research Holtz develops dihydrotachysterol,[21] a synthetic analog of vitamin D that does not require renal activation like vitamin D2 or vitamin D3.[22]
1936 Research Cholecalciferol is first described.[23] Also known as vitamin D3, it is a type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement.[24]
1936 Skin cancer Research S. Peller observes that U.S. Navy personnel who experiences skin cancer has a much lower incidence of nonskin cancers. This leads him to hypothesize that the development of skin cancer confers protection against other cancers. This marks the beginning of the emergence of the epidemiologic role of sunlight in cancer prevention.[1] United States
1937 Rickets Research The term "rickets resistant to vitamin D" is coined by Albright et al., as the patients they describe present with changes in mineral metabolism that could only be overcome by very large daily doses of vitamin D.[11]
1937 Research German chemist Adolf Windaus and colleagues discover 7-Dehydrocholesterol (7- DHC), the precursor of vitamin D3, by isolating 7-DHC from animal skin and inducing formation of vitamin D3 by irradiating 7-DHC with ultraviolet radiation. Windaus would receive the Nobel Prize in Chemistry in 1939 for this work, which unifies two apparently disparate lines of evidence through the discovery that exposure to UV is responsible for vitamin D synthesis.[1] Germany
1937 Research The isolation and identification of the vitamin D nutritional compounds are completed, drawing to a close an important era of vitamin D investigation.[25]
1940 Recommendation The first recommendation for vitamin D is established in the United States, determining the value of 400 IU (i.e., the lower value of a range for infants at the time), for adults in a footnote only, that states “When not available from sunshine, [vitamin D] should be provided up to the minimal amounts recommended for infants”.[4] United States
1942 Cancer (internal) Research Apperly first observes that there are lower overall mortality rates from internal cancers in sunnier regions of the United States.[1] United States
1946 Lupus vulgaris Research Dowling et al. report the treatment of patients with lupus vulgaris with oral vitamin D. Eighteen of 32 patients appear to be cured, with nine improved.[2]
1952 Product launch Synthetic vitamin D2 and D3 compounds start being produced.[5]
1953–1955 Notable case Nutrition surveys indicate that the normal British infant could ingest from various sources as much as 4,000 IU of vitamin D per day. This is coincident with numerous cases of infantile hypercalcemia mainly of the mild form. In the following years the food enrichment policies would change and subsequently make the incidence of infantile hypercalcemia fall.[26] United Kingdom
1955 Research The complete photochemical and thermal reaction steps from ergosterol to calciferol are elucidated by Velluz et al.[12] France
1957 Recommendation The American Medical Association’s Council on Foods and Nutrition recommends that milk should contain 400 IU (10 μg) per quart and that the vitamin D content be measured at least twice yearly by an independent laboratory.[4] United States
1958 Diabetes Research In a British birth cohort study, calcifediol is inversely associated with prevalent elevated hemoglobin A1c.[27] United Kingdom (Institute of Child Health, London)
1960s Skin cancer Notable case An increasing trend of skin cancer incidence rates starts being observed from this time, leading to large sun-safety campaigns.[4]
1960 Research 25,26-Dihydroxyvitamin D3(25,26-dihydroxycholecalciferol) becomes the first dihydroxylated metabolite to be identified.[28] It is a metabolite of vitamin D3 with intestinal calcium transport activity.[29]
1960s Supravalvular stenosis Research During this time, vitamin D is considered the cause of supravalvular stenosis.[4] The published hypothesis is that “toxic” amounts of vitamin D during pregnancy gave rise to a clinical condition titled “infantile hypercalcemia syndrome”.[30]
1963 Recommendation The American Academy of Pediatrics (AAP) Committee on Nutrition recommends a dose of vitamin D of 10 micrograms (400 IU) daily as the standard of care for children.[31]
1963 Recommendation The US Food and Drug Administration's Daily Recommended Allowance of vitamin D is determined to be 400 IU, consistent with the recommendations of the American Academy of Pediatrics (AAP) Committee on Nutrition.[32] United States
1963 Recommendation The American Academy of Pediatrics Committee on Nutrition recommends that all infants receive 10μg (400 IU) of vitamin D per day.[11] United States
1965–1975 Research In this period, the elements of the vitamin D endocrine system that regulate calcium and phosphorus become clear.[33]
Mid–1960s Research New techniques using radioactively labeled substances are developed. Before this, scientists did not have the tools to follow vitamin D metabolism in living subjects.[11]
1966 Research Wasserman and his colleagues discover the existence of a calcium-binding protein in the intestines of chicks given vitamin D.[25]
1967 Research Loomis suggests that melanin pigmentation evolved for protection from vitamin intoxication because of excessive exposure to sunlight.[4]
1968 Research Team led by Hector DeLuca at the University of Wisconsin isolate an active substance identified as 25-hydroxyvitamin D3, which the team later proves to be produced in the liver.[11] United States
1968 Kidney disease Research The idea that vitamin D might function as a steroid-like hormone emerges.[5]
1968–1971 Research During this period, researchers make great progress in understanding the metabolic processing of vitamin D and its physiological activity.[11]
1969 Research The vitamin D receptor (VDR) is discovered in the intestine of vitamin D deficient chicks.[5]
1969 Research The chemical synthesis of calcifediol is determined by J. W. Blunt and Hector F. DeLuca.[25][34] United States
1971 Research Calcitriol, an active form of vitamin D, is identified by American adult endocrinologist Michael F. Holick working in the laboratory of Hector DeLuca.[35][36] United States
1971 Research D. R. Fraser and E. Kodicek first identify the kidney as the source of calcitriol.[37]
1972 Research The chemical synthesis of 1α,25-(OH)2D3 (calcitriol) is achieved.[25]
1974 Rheumatoid arthritis Research Researchers report vitamin D deficiency in postmenopausal women with rheumatoid arthritis who have suffered fractures compared with postmenopausal women with rheumatoid arthritis who have not suffered fractures.[38]
1974 Research The existence of a chromosomal receptor for vitamin D is demonstrated.[11]
1975 Research Mark Haussler at the University of Arizona discovers a protein receptor that binds calcitriol to the nucleus of cells in the intestine.[11][39] United States
1977 Research A report from the laboratory of Elsie Widdowson in Cambridge, England, describes a new form of water-soluble vitamin D in human milk. This metabolite, vitamin D sulfate, is present at concentrations of 400–950 IU/L. This would prompt the gained credibility of the idea that breast-fed infants do not need supplemental vitamin D.[31] United Kingdom
1979 Literature Anthony W. Norman publishes Vitamin D: The Calcium Homeostatic Steroid Hormone.[40]
1980 Research Holick et al. report on the exact sequence of steps leading to the photoproduction of cholecalciferol in the skin.[12][41] United States
1980 Short gestation and low birth weight Research In response to recognition of a high incidence of pregnancy-associated osteomalacia and decreased fetal size in association with vitamin D deficiency among Asian (primarily Indian) women in England, O.G. Brooke et al. evaluate vitamin D supplementation in Asian women. The study includes 59 pregnant women given 1,000 IU/day in their last trimester and a matched group of 67 women given placebo. The researchers report modest increase in birth weight of 123 g in the treatment group.[42] United Kingdom
1980 Cancer Research (theory) The solar UVB/vitamin D/cancer theory is proposed by brothers Cedric Garland and Frank C. Garland. The researchers hypothesize that the potential benefit of sun exposure is attributed to vitamin D. Initially, the hypothesis is centered on colon cancer, but later it is extended to breast cancer, ovarian cancer, prostate cancer, and to multiple cancer types.[43] United States
1980 Hypocalcemia, secondary hyperparathyroidism, osteodystrophy, rickets, osteomalacia Drug launch Alfacalcidol is first introduced in Canada. It is a vitamin D analogue used for the management of hypocalcemia, secondary hyperparathyroidism, and osteodystrophy in patients with chronic renal failure, as well as some types of rickets and osteomalacia.[44] Canada
1980 Birth weight Research R. K. Marya et al. study 25 pregnant women treated with 1,200 IU of vitamin D a day in their third trimester, 20 women treated with two doses of 600,000 IU in the seventh and eighth months of pregnancy, and 75 women who received no supplemental vitamin D. The researchers report a significantly greater increase in birth weight with either vitamin D supplementation, but greater increase with the 600,000 IU doses.[45]
1980 Cancer (colon) Research C. F. Garland and F. C. Garland publish a seminal article on the relationship between vitamin D, calcium and colon cancer risk in the International Journal of Epidemiology. In this ecologic analysis, they propose that vitamin D and calcium are protective factors against colon cancer.[1] The authors also find a clear positive association between latitude and mortality from colon cancer in the United States. They hypothesize that this might be related to sun-induced vitamin D.[46] United States
1980 Research Michael F. Holick describes the dermal synthesis of vitamin D.[19] United States
1981 Cardiovascular disease Research Drawing on ecological studies of variations in cardiovascular disease by season, latitude, and altitude, Robert Scragg publishes a hypothesis that sunlight and vitamin D may protect against cardiovascular disease.[47] Australia
1981 Cancer (melanoma, leukemia) Research The classical consideration of vitamin D as a regulator of calcium and phosphate metabolism and bone biology begins when David Feldman’s[48] and Tatsuo Suda’s[49] groups show that the most active vitamin D metabolite, calcitriol, inhibits the proliferation of melanoma cells and induces the differentiation of leukemic cells.[4]
1981 Cystic fibrosis Research Reduced vitamin D binding protein levels in people with cystic fibrosis is first reported.[2]
1982 Rickets Research The role of the vitamin D receptor in vitamin D-dependent rickets type-2 is realized.[11]
1983 Research S. H. Sedrani et al. find unexpectedly low vitamin D levels in Saudi university students as well as in elderly subjects suggesting that up to 100% of the Saudi population may have vitamin D deficiency or insufficiency.[50] Saudi Arabia
1984 Kidney disease Research Research by B. P. Halloran et al. reports conclusive evidence of the importance of correcting the impaired 25(OH)D availability in chronic kidney disease.[51]
1984 Breastfeeding Research In a study, Greer et al. expose lactating white women to UVB exposure equivalent to 30 min of sunshine at midday on a clear summer day at temperate latitudes. With this exposure, the vitamin D content of the milk significantly increases with a peak at 48 h and with a return to baseline at 7 days.[52]
1984 Research A paper by Narang et al. states that 2,400 IU/day is the dose of vitamin D that statistically increases serum calcium, but not quite into the hypercalcemia range.[4]
1985 Tuberculosis, pulmonary disease Research A study conducted on 40 Indonesian patients with active tuberculosis and treated with anti-tuberculosis chemotherapy, reports that 10 patients with the highest calcifediol levels at the outset of therapy had “less active pulmonary disease”.[2] Indonesia
1985 Tuberculosis Research Davies observes that people migrating to the United Kingdom from countries with a high incidence of latent Mycobacterium tuberculosis infection experience rates of active tuberculosis that exceeds rates in their countries of origin, and that this increased risk coincide with the development of vitamin D deficiency, probably arising as a result of decreased sun exposure.[2] United Kingdom
1985 Psoriasis Research S. Morimoto and Y. Kumahara report that a patient who was treated orally with 1α-hydroxyvitamin D3 for osteoporosis had a dramatic remission of psoriatic skin lesions.[53] Japan (Osaka University)
1986 Mycobacterium tuberculosis Research Experiments by Rook become the first to suggest vitamin D-induced antimicrobial activity by human monocytes and macrophages against Mycobacterium tuberculosis.[4]
1986 Cancer (melanoma, leukemia) Research Colston et al. become the first to demonstrate that 1α,25(OH)2D3 (calcitriol) inhibits human melanoma cell proliferation significantly in vitro at nanomolar concentrations. Parallel studies in the same year also find that 1α25(OH)2D3 could induce differentiation in cultured mouse and human myeloid leukemia cells.[54]
1987 Research Molecular cloning of the cDNA encoding chick vitamin D receptor is achieved for the first time by McDonnell et al.[11]
1988 Research The successful cloning of the cDNA encoding the human vitamin D receptor is achieved.[11]
1988 Research A research group led by Bert W. O'Malley from California Biotechnology Inc. manages to clone the vitamin D receptor.[11] United States
1989 Kidney disease (hyperparathyroidism) Drug launch Paricalcitol is patented. It is an analog of 1,25-dihydroxyergocalciferol, the active form of vitamin D2 (ergocalciferol).[55] It is a vitamin D analog used to treat hyperparathyroidism associated with stage 3 or greater chronic kidney disease.[56] United States
1989 Program launch DEQAS (Vitamin D External Quality Assessment Scheme) is launched to compare the performance of assays for vitamin D measurement. It monitors the performance of 25-hydroxyvitamin D (25-OHD) and 1,25- dihydroxyvitamin D (1,25(OH)2D) assays.[57] DEQAS would grow to be the dominant proficiency testing scheme with more than 470 laboratories participating from over 30 countries.[4]
1989 Cancer (breast and colon) Research E.D. Gorham et al. postulate an association between ultraviolet-B blocking air pollution and increased risk of breast and colon cancer, based on inhibition by sulfurrelated air pollution of cutaneous vitamin D photosynthesis, resulting in vitamin D deficiency.[58][1]
1989 Research The sequence elements in the human osteocalcin gene conferring basal activation and inducible response of this gene promoter to hormonal 1,25(OH) 2 D 3 are described.[5]
1989 Recommendation The US Recommended Dietary Allowance (RDA) of vitamin D is determined at 200 IU to guarantee a protecting effect against malignancies and other diseases. However, several subsequent investigations would show that 200 IU/day has no effect on bone status, with adults needing five times the RDA, or 1,000 IU, to adequately prevent bone fractures, protect against some malignancies, and derive other broad-ranging health benefits.[4] United States
1989 Cancer (colon) Research Garland et al. report that prediagnostic serum 25(OH)D concentration inversely correlates with colon cancer.[19]
1990 Cancer (prostate) Research Researchers note that the major risk factors for prostate cancer, older age, Black race, and residence at northern latitudes, are all associated with a decreased synthesis of vitamin D.[4]
1990 Psoriasis Product launch Vitamin D derivative calcipotriol is first introduced as ointment for the treatment of psoriasis in Denmark. It is a synthetic derivative of calcitriol.[59] Denmark
1992 Research A review from M. J. McKenna summarizing the knowledge from 1971–1990 on worldwide vitamin D status, concludes that oral vitamin D intake is lower in Western and Central Europe (2–3 μg/day) than in both North America (5.5–7 μg/day) and Scandinavia (4–6 μg/day) due to a higher ingestion of vitamin D supplementation in Scandinavia and a higher intake of natural sources of vitamin D, such as fatty fish. Plasma 25(OH)D varies with season in both young adults and elderly and is lower during the winter and throughout the year in Central Europe (∼ 18 nmol/l) than in both North America (∼ 58 nmol/l) and Scandinavia (∼ 37 nmol/l). McKenna also concludes that hypovitaminosis D and related skeletal abnormalities are most common in elderly residents in Europe, but are reported in all elderly populations.[60]
1992 Cancer (prostate cancer) Research Geographic analyses show that U.S. county-wide mortality rates for prostate cancer among Caucasian men are inversely correlated with the availability of ultraviolet radiation, the major source of vitamin D.[61][62] United States
1993 Psoriasis Product launch Tacalcitol ointment is first approved in Japan.[59] Tacalcitol (1,24-dihydroxyvitamin D3) is a synthetic vitamin D3 analog.[63] It is prescribed for the treatment of psoriasis.[64] Japan
1994–1999 Muscle function, bone, and fracture risk Research A study conducted in this period in Montreal of blood samples from 256 elderly (aged 65–94 years) apparently healthy, community-dwelling men and women, shows a very surprising 32% of women and 51% of men with 25(OH)D levels below 20 nmol/l[65]. This level of deficiency is likely to have an adverse effect on muscle function, bone, and fracture risk.[4] Canada
1995 Research Dutch research team led by R. P. van der Wielen measure wintertime plasma 25(OH)D (calcifediol) in 824 elderly people from 11 European countries. The team concludes that freeliving elderly Europeans, regardless of geographical location, are at substantial risk of inadequate vitamin D status during winter. Unexpectedly, the lowest mean 25(OH)D concentrations are seen in Southern Europe.[66] Europe
1997 Research As the result of 25 years of research, the cytochrome P450, CYP27B1, representing the 1α-Hydroxylase enzyme is finally cloned from a rat renal cDNA library by St Arnaud’s group in Montreal.[67] 1α-Hydroxylase is the key enzyme in vitamin D metabolism.[68] Canada
1997 Research Vitamin D5 is first synthesized by researchers at the Department of Chemistry at the University of Chicago.[69]
1997 Recommendation The American Academy of Pediatrics and the Canadian Pediatric Association both recommend 400 IU/day of vitamin D, which is twice what the Institute of Medicine (IOM) of the US National Academy of Sciences recommend in the same year.[4] United States
1997 Recommendation The dietary reference intake panel for calcium, phosphorus, magnesium, vitamin D and fluoride is first established to provide intake recommendations for Americans and Canadians.[70][19] United States, Canada
1997 Recommendation The U.S. Institute of Medicine (IOM) designates 2,000 IU/day as the TUIL (tolerable upper intake level) of vitamin D intake.[4] United States
1997 Research Researchers manage to clone the human 25-Hydroxyvitamin D 1-alpha-hydroxylase, a secosteroid hormone which plays a crucial role in normal bone growth, calcium metabolism, and tissue differentiation.[71] United States
1997 Research The Norwegian National Dietary Survey shows that the vitamin D intake is 13% larger in north than in south Norway. This suggests that there is no significant north–south gradient in the level of vitamin D metabolites in serum in that country.[4] Norway
1997 Recommendation The American Academy of Pediatrics (AAP) Committee on Nutrition recommends a dose of vitamin D 400 IU daily as the standard of care for children.[4] United States
1998 Kidney disease (hyperparathyroidism) Drug launch Paricalcitol (marketed under the trade name Zemplar) is introduced by Abbott Laboratories.[72] United States
1998 Cancer (prostate cancer) Research It is demonstrated that normal human prostate cells possess 25-hydroxyvitamin D3–1α-hydroxylase (1α(OH)ase) and indeed synthesize 1,25(OH)2D from 25(OH)D.[73] United States (University of Miami School of Medicine)
1999 Asthma, allergy Research Wjst and Dold, in trying to explain the rise in asthma and allergy rates, propose their hypothesis that the introduction of vitamin D in fortified foods and in multivitamin preparations in many westernized countries is related to the asthma and allergy epidemic in these countries.[2] They propose that vitamin D supplementation might be the cause of global increases in asthma and allergies.[74]
1999 Literature Michael F. Holick publishes Vitamin D: Molecular Biology, Physiology, and Clinical Applications.[75] United States
2000 Cancer (prostate cancer) Research Researchers show that 25(OH)D (calcifediol) inhibits the proliferation of prostate cells that possess 1α-OHase.[76] United States (Wake Forest School of Medicine, Winston-Salem, North Carolina)
2001 Kidney disease (secondary hyperparathyroidism) Drug launch Doxercalciferol (marketed under the trade name Hectorol) is first introduced in Canada by Sanofi Genzyme. It is a synthetic vitamin D2 analog used to treat secondary hyperparathyroidism in patients with chronic kidney disease with or without therapy of dialysis.[77] Canada
2003 Recommendation In response to the vitamin D adequate intake recommendations made by the Institute of Medicine in 1997, the Committee on Nutrition of the American Academy of Pediatrics recommends 200 IU/d vitamin D for all infants and children.[31] United States
2005 Literature David Feldman, J. Wesley Pike and Francis H. Glorieux publish Vitamin D, which includes over 100 chapters covering from chemistry and metabolism to mechanisms of action, diagnosis and management, new analogs, and emerging therapies involving vitamin D.[78]
2006 Cancer (digestive-system) Research A study by researchers at Harvard Medical School, analizing 1095 men and documents from 1986 through 2000 of 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer, concludes that low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers.[79] United States
2007 Cancer (breast Research Garland et al. publish a breast cancer doseresponse meta-analysis, finding that individuals with the highest blood levels of 25-hydroxyvitamin D has reduced risk of breast cancer.[80][1] United States
2007 Anaphylaxis Research Camargo and colleagues propose that vitamin D status might influence risk of food-induced anaphylaxis (FIA) after observing a strong north–south gradient in epinephrine autoinjector prescription rates in the United States.[81] United States (Boston)
2007 Psoriasis Drug launch CollaGenex Pharmaceuticals licenses becocalcidiol, a vitamin D analogue for topical treatment of psoriasis and psoriatic disorders.[82][83] United States
2008 Skin cancer Literature Jörg Reichrath publishes Sunlight, Vitamin D and Skin Cancer, which provides an overview of positive and negative effects of ultraviolet-exposure, with a focus on Vitamin D and skin cancer.[84]
2008 Recommendation The American Academy of Pediatrics increases the recommended supplementation dose from 200 to 400 IU daily across the pediatric age spectrum.[85] United States
2008 Literature James Dowd and Diane Stafford publish The Vitamin D Cure.[86]
2009 Literature Soram Khalsa publishes Vitamin D Revolution.[87]
2010 Pneumonia Research A randomized clinical trial finds that vitamin D supplementation reduces the risk of pneumonia in children.[19]
2010 Rheumatoid arthritis Research A study in Italy inversely relates rheumatoid arthritis activity and disability scores with calcifediol concentrations.[19] Italy
2011 (January) Osteoporosis Drug launch Eldecalcitol is approved in Japan, for the treatment for osteoporosis.[88] It is an analog of vitamin D.[89] Japan
2012 Literature Ian Wishart publishes Vitamin D: Is This the Miracle Vitamin?, which claims that taking vitamin D reduces up to a 77% the risk of developing cancer.[90]
2016 Literature Ana Claudia Domene publishes Multiple Sclerosis and (lots Of) Vitamin D, which introduces the Coimbra Protocol, a therapeutic approach that relies on high doses of vitamin D with the purpose to boost the immune system.[91]
2018 Cancer (colorectal) Research A study by an international group of researchers using data from about 12,800 people finds that higher levels of vitamin D in the blood is associated with a lower risk for getting colorectal cancer.10.1093/jnci/djy087[92]
2018 Literature Emilia Pauline Liao publishes Extraskeletal Effects of Vitamin D: A Clinical Guide, which provides an examination of extraskeletal effects of vitamin D and the associations between vitamin D deficiency and various disease states.[93]
2020 (July) COVID-19 Literature David C. Anderson and David S. Grimes publish Vitamin D Deficiency and Covid-19: Its Central Role in a World Pandemic, which emphasizes the immunity provided by adequate levels of Vitamin D against the invasion by all new viruses.[94]
2021 (January 14) Common cold, influenza, influenza-like illness Research A randomized controlled trial of vitamin D supplements led by QIMR Berghofer Medical Research Institute in Australia finds they do not protect most people from developing colds, influenza and other acute respiratory infections.[95] Australia

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References

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