Timeline of vitamin D

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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

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Mohr, Sharif B. (February 2009). "A Brief History of Vitamin D and Cancer Prevention". Annals of Epidemiology. 19 (2): 79–83. doi:10.1016/j.annepidem.2008.10.003. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Litonjua, Augusto A. (23 May 2012). Vitamin D and the Lung: Mechanisms and Disease Associations. Springer Science & Business Media. ISBN 978-1-61779-888-7. 
  3. ↑ Milne, G. W. A.; Delander, M. (2008). Vitamin D Handbook: Structures, Synonyms, and Properties. John Wiley & Sons. ISBN 978-0-470-13983-7. Retrieved 31 August 2021. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 Holick, Michael F. (23 April 2010). "Vitamin D: Physiology, Molecular Biology, and Clinical Applications". Humana Press. Retrieved 16 August 2021. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Torres, Pablo A. Ureña; Cozzolino, Mario; Vervloet, Marc G. (21 September 2016). Vitamin D in Chronic Kidney Disease. Springer. ISBN 978-3-319-32507-1. 
  6. ↑ Whiting, Susan J.; Calvo, Mona S. (1 February 2005). "Dietary Recommendations for Vitamin D: a Critical Need for Functional End Points to Establish an Estimated Average Requirement". The Journal of Nutrition. 135 (2): 304–309. doi:10.1093/jn/135.2.304. 
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  40. ↑ Norman, Anthony W. (1979). Vitamin D: The Calcium Homeostatic Steroid Hormone. Academic Press. ISBN 978-0-12-521050-8. 
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  42. ↑ Brooke, O G; Brown, I R; Bone, C D; Carter, N D; Cleeve, H J; Maxwell, J D; Robinson, V P; Winder, S M (15 March 1980). "Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth.". BMJ. 280 (6216): 751–754. doi:10.1136/bmj.280.6216.751. 
  43. ↑ Reichrath, Jörg (11 September 2020). Sunlight, Vitamin D and Skin Cancer. Springer Nature. ISBN 978-3-030-46227-7. 
  44. ↑ "Alfacalcidol". go.drugbank.com. Retrieved 23 September 2021. 
  45. ↑ Marya, R.K.; Rathee, S.; Lata, V.; Mudgil, S. (1981). "Effects of Vitamin D Supplementation in Pregnancy". Gynecologic and Obstetric Investigation. 12 (3): 155–161. doi:10.1159/000299597. 
  46. ↑ Garland, Cedric F; Garland, Frank C (1980). "Do Sunlight and Vitamin D Reduce the Likelihood of Colon Cancer?". International Journal of Epidemiology. 9 (3): 227–231. doi:10.1093/ije/9.3.227. 
  47. ↑ Scragg, Robert (1981). "Seasonality of Cardiovascular Disease Mortality and the Possible Protective Effect of Ultra-violet Radiation". International Journal of Epidemiology. 10 (4): 337–341. doi:10.1093/ije/10.4.337. 
  48. ↑ Colston, Kay; Colston, M. Joseph; Feldman, David (March 1981). "1,25-DIHYDROXYVITAMIN D 3 AND MALIGNANT MELANOMA: THE PRESENCE OF RECEPTORS AND INHIBITION OF CELL GROWTH IN CULTURE". Endocrinology. 108 (3): 1083–1086. doi:10.1210/endo-108-3-1083. 
  49. ↑ Abe, E.; Miyaura, C.; Sakagami, H.; Takeda, M.; Konno, K.; Yamazaki, T.; Yoshiki, S.; Suda, T. (1 August 1981). "Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3.". Proceedings of the National Academy of Sciences. 78 (8): 4990–4994. doi:10.1073/pnas.78.8.4990. 
  50. ↑ Sedrani, S H; Elidrissy, A W; El Arabi, K M (1 July 1983). "Sunlight and vitamin D status in normal Saudi subjects". The American Journal of Clinical Nutrition. 38 (1): 129–132. doi:10.1093/ajcn/38.1.129. 
  51. ↑ Halloran, Bernard P.; Schaefer, Phillip; Lifschitz, Meyer; Levens, Marilyn; Goldsmith, Ralph S. (December 1984). "Plasma Vitamin D Metabolite Concentrations in Chronic Renal Failure: Effect of Oral Administration of 25-Hydroxyvitamin D3*". The Journal of Clinical Endocrinology & Metabolism. 59 (6): 1063–1069. doi:10.1210/jcem-59-6-1063. 
  52. ↑ Greer, Frank R.; Hollis, Bruce W.; Cripps, Derek J.; Tsang, Reginald C. (September 1984). "Effects of maternal ultraviolet B irradiation on vitamin D content of human milk". The Journal of Pediatrics. 105 (3): 431–433. doi:10.1016/s0022-3476(84)80021-9. 
  53. ↑ Morimoto, S; Kumahara, Y (March 1985). "A patient with psoriasis cured by 1 alpha-hydroxyvitamin D3.". Medical journal of Osaka University. 35 (3-4): 51–4. PMID 4069059. 
  54. ↑ Gombart, Adrian F. (21 November 2012). Vitamin D: Oxidative Stress, Immunity, and Aging. CRC Press. ISBN 978-1-4398-5021-3. 
  55. ↑ Fischer, János; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. ISBN 978-3-527-60749-5. 
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  58. ↑ Gorham, ED; Garland, CF; Garland, FC (March 1989). "Acid haze air pollution and breast and colon cancer mortality in 20 Canadian cities.". Canadian journal of public health = Revue canadienne de sante publique. 80 (2): 96–100. PMID 2720547. 
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  63. ↑ Peters DC, Balfour JA (August 1997). "Tacalcitol". Drugs. 54 (2): 265–71; discussion 272. PMID 9257082. doi:10.2165/00003495-199754020-00005. 
  64. ↑ Lecha, M; Mirada, A; Lopez, S; Artes, M (July 2005). "ORIGINAL ARTICLE. Tacalcitol in the treatment of psoriasis vulgaris: the Spanish experience.". Journal of the European Academy of Dermatology and Venereology. 19 (4): 414–417. doi:10.1111/j.1468-3083.2005.01099.x. 
  65. ↑ Vecino-Vecino, Concepción; Gratton, Miren; Kremer, Richard; Rodriguez-Mañas, Leocadio; Duque, Gustavo (2006). "Seasonal Variance in Serum Levels of Vitamin D Determines a Compensatory Response by Parathyroid Hormone: Study in an Ambulatory Elderly Population in Quebec". Gerontology. 52 (1): 33–39. doi:10.1159/000089823. 
  66. ↑ van der Wielen, R.P.J.; de Groot, L.C.P.G.M.; van Staveren, W.A.; Löwik, M.R.H.; van den Berg, H.; Haller, J.; Moreiras, O. (July 1995). "Serum vitamin D concentrations among elderly people in Europe". The Lancet. 346 (8969): 207–210. doi:10.1016/s0140-6736(95)91266-5. 
  67. ↑ St-Arnaud, René; Messerlian, Serge; Moir, Janet M.; Omdahl, John L.; Glorieux, Francis H. (1 October 1997). "The 25-Hydroxyvitamin D 1-Alpha-Hydroxylase Gene Maps to the Pseudovitamin D-Deficiency Rickets (PDDR) Disease Locus". Journal of Bone and Mineral Research. 12 (10): 1552–1559. doi:10.1359/jbmr.1997.12.10.1552. 
  68. ↑ Brenza, H. L.; Kimmel-Jehan, C.; Jehan, F.; Shinki, T.; Wakino, S.; Anazawa, H.; Suda, T.; DeLuca, H. F. (17 February 1998). "Parathyroid hormone activation of the 25-hydroxyvitamin D3-1 -hydroxylase gene promoter". Proceedings of the National Academy of Sciences. 95 (4): 1387–1391. doi:10.1073/pnas.95.4.1387. 
  69. ↑ Moriarty, Robert M.; Albinescu, Dragos (September 2005). "Synthesis of 1α-Hydroxyvitamin D 5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation". The Journal of Organic Chemistry. 70 (19): 7624–7628. doi:10.1021/jo050853f. 
  70. ↑ "Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride". 17 September 1997. doi:10.17226/5776. 
  71. ↑ Fu, Glenn K.; Lin, Dong; Zhang, Martin Y. H.; Bikle, Daniel D.; Shackleton, Cedric H. L.; Miller, Walter L.; Portale, Anthony A. (December 1997). "Cloning of Human 25-Hydroxyvitamin D-1α-Hydroxylase and Mutations Causing Vitamin D-Dependent Rickets Type 1". Molecular Endocrinology. 11 (13): 1961–1970. doi:10.1210/mend.11.13.0035. 
  72. ↑ "Paricalcitol". go.drugbank.com. Retrieved 21 September 2021. 
  73. ↑ Schwartz, GG; Whitlatch, LW; Chen, TC; Lokeshwar, BL; Holick, MF (May 1998). "Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3.". Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 7 (5): 391–5. PMID 9610788. 
  74. ↑ Hewison, Martin; Bouillon, Roger; Giovannucci, Edward; Goltzman, David (14 December 2017). Vitamin D: Volume 2: Health, Disease and Therapeutics. Academic Press. ISBN 978-0-12-809964-3. 
  75. ↑ Holick, Michael F. (1999). Vitamin D: Molecular Biology, Physiology, and Clinical Applications. Humana Press. ISBN 978-0-89603-467-9. 
  76. ↑ Barreto, AM; Schwartz, GG; Woodruff, R; Cramer, SD (March 2000). "25-Hydroxyvitamin D3, the prohormone of 1,25-dihydroxyvitamin D3, inhibits the proliferation of primary prostatic epithelial cells.". Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 9 (3): 265–70. PMID 10750664. 
  77. ↑ "Doxercalciferol". go.drugbank.com. Retrieved 21 September 2021. 
  78. ↑ Feldman, David; Pike, J. Wesley; Glorieux, Francis H. (25 January 2005). Vitamin D. Elsevier. ISBN 978-0-08-054364-2. 
  79. ↑ Giovannucci, Edward; Liu, Yan; Rimm, Eric B.; Hollis, Bruce W.; Fuchs, Charles S.; Stampfer, Meir J.; Willett, Walter C. (5 April 2006). "Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men". JNCI: Journal of the National Cancer Institute. 98 (7): 451–459. doi:10.1093/jnci/djj101. 
  80. ↑ Garland, Cedric F.; Gorham, Edward D.; Mohr, Sharif B.; Grant, William B.; Giovannucci, Edward L.; Lipkin, Martin; Newmark, Harold; Holick, Michael F.; Garland, Frank C. (March 2007). "Vitamin D and prevention of breast cancer: Pooled analysis". The Journal of Steroid Biochemistry and Molecular Biology. 103 (3-5): 708–711. doi:10.1016/j.jsbmb.2006.12.007. 
  81. ↑ Vassallo, M. F.; Banerji, A.; Rudders, S. A.; Clark, S.; Camargo, C. A. (November 2010). "Season of birth and food-induced anaphylaxis in Boston: ALLERGYNet". Allergy. 65 (11): 1492–1493. doi:10.1111/j.1398-9995.2010.02384.x. 
  82. ↑ "Becocalcidiol". go.drugbank.com. Retrieved 21 September 2021. 
  83. ↑ "The Biologics News and Reports Portal". pipelinereview. Retrieved 21 September 2021. 
  84. ↑ Reichrath, Jörg (11 September 2020). Sunlight, Vitamin D and Skin Cancer. Springer Nature. ISBN 978-3-030-46227-7. 
  85. ↑ Wagner, C. L.; Greer, F. R. (1 November 2008). "Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents". PEDIATRICS. 122 (5): 1142–1152. doi:10.1542/peds.2008-1862. 
  86. ↑ MD, James Dowd; Stafford, Diane (14 January 2008). The Vitamin D Cure. John Wiley & Sons. ISBN 978-0-470-13155-8. 
  87. ↑ M.D, Soram Khalsa (1 March 2009). Vitamin D Revolution. Hay House, Inc. ISBN 978-1-4019-2911-4. 
  88. ↑ Bronson J, Dhar M, Ewing W, Lonberg N (2012). "To Market — 2011: Eldecalcitol (osteoporosis)". In Desai MC. Annual Reports in Medicinal Chemistry. 47 (1st ed.). San Diego: Elsevier Inc. pp. 529–531. ISBN 9780123964922. 
  89. ↑ Hatakeyama, Susumi; Yoshino, Madoka; Eto, Kohei; Takahashi, Keisuke; Ishihara, Jun; Ono, Yoshiyuki; Saito, Hitoshi; Kubodera, Noboru (July 2010). "Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]". The Journal of Steroid Biochemistry and Molecular Biology. 121 (1-2): 25–28. doi:10.1016/j.jsbmb.2010.03.041. 
  90. ↑ Wishart, Ian (2012). Vitamin D: Is This the Miracle Vitamin?. Howling at the Moon Publishing. ISBN 978-0-9876573-1-2. 
  91. ↑ Domene, Ana Claudia (18 February 2016). Multiple Sclerosis and (lots Of) Vitamin D: My Eight-Year Treatment with The Coimbra Protocol for Autoimmune Diseases. CreateSpace Independent Publishing Platform. ISBN 978-1-5191-6531-2. 
  92. ↑ "Vitamin D Levels Linked to Lower Colorectal Cancer Risk". www.cancer.org. Retrieved 20 September 2021. 
  93. ↑ Liao, Emilia Pauline (23 April 2018). Extraskeletal Effects of Vitamin D: A Clinical Guide. Humana Press. ISBN 978-3-319-73742-3. 
  94. ↑ Vitamin D Deficiency and Covid-19: Its Central Role in a World Pandemic. ISBN 0956213278. 
  95. ↑ "Clinical trial finds vitamin D does not ward off colds and flu". medicalxpress.com. Retrieved 19 March 2021. 
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