Timeline of vitamin D

From Timelines
Revision as of 21:34, 16 September 2021 by Sebastian (talk | contribs)
Jump to: navigation, search

This is a timeline of vitamin D.

Sample questions

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

Big picture

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.[1]
1920s Discovery Vitamin D is discovered during research into the causes and treatment of rickets.[2][3]
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” [4]
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"[5] ". 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"[6]

Numerical and visual data

Country and date Age groupings Recommended value
y ug (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" Nonve 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
2021 19
Vitamin d.png

Full timeline

Year Month and date Event type Details
2nd century AD Soranus of Ephesus’s describes rickets in Roman children.[5]
1650 Rickets, the bone disease caused by vitamin D deficiency, is described in detail by British physician Francis Glisson.[8]
1770 Cod liver oil, rich in vitamin D, is first advocated for the treatment of tuberculosis.[9] Derived from liver of cod fish (Gadidae), today it is a dietary supplement.
1822 Sniadecki observes that lack of sunlight exposure is likely a cause of rickets.[4]
1824 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.[8]
1849 "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."[10]
1849 Cod liver oil is recognized in Europe as beneficial in the treatment of tuberculosis.[4] Europe
1890 British medical missionary and epidemiologist Theodore Palm notes through his travels that children living in equatorial countries do not develop rickets.[1]
1903 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 English biochemist Frederick Gowland Hopkins postulates the existence of essential dietary factors necessary for the prevention of diseases such as scurvy or rickets.[8]
1912 Scientific development Hopkins describes the vitamins.[5]
1914 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]
1919 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.[11] United Kingdom
1921 Hess and Unger observe that “seasonal incidence of rickets is due to seasonal variations of sunlight.”[8]
1922 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 "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."[8]
1923 Scientific development Goldblatt and Soames show the conversion of a precursor to vitamin D in the skin under the effect of ultraviolet light.[5]
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.” [3]
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).” "[8]
1930 “vitamin D2 has been used as a dietary supplement in lieu of vitamin D3 since the 1930s” [4]
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” [4]
1931 Vitamin D2 is purified and crystallized simultaneously by researchers in London and the Netherlands.[2][8] United Kingdom, Netherlands
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)"[11]
1936 Cholecalciferol is first described.[12]
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” [3]
1936 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 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.[5]
1937 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 “Bunker and Harris reported in 1937 that the most effective wavelength for curing rickets in rats was 297 nm” [4]
1930s “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” [4]
1930 “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” [4]
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” [4]
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”” [4]
1942 Apperly first observes that there are lower overall mortality rates from internal cancers in sunnier regions of the United States.[1] United States
1946 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]
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)”[4]
1952 Synthetic vitamin D2 and D3 compounds start being produced.[6]
1955 "The complete photochemical and thermal reaction steps from ergosterol to calciferol were elucidated only in 1955 by Velluz et al."[8] France
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” [4]
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” [4]
1950s “In the 1950s, there was an outbreak of presumed vitamin D intoxication in infants and young children” [4]
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” [4]
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” [4]
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”” [4]
1960 “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” [4]
1960 “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.” [4]
1963 “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” [4]
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” [4]
1963 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.[13]
1963 “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” [4]
1963 Recommendation The American Academy of Pediatrics Committee on Nutrition recommends that all infants receive 10μg (400 IU) of vitamin D per day.[5]
1965–1975 In this period, the elements of the vitamin D endocrine system that regulate calcium and phosphorus become clear.[14]
1967 Loomis suggests that melanin pigmentation evolved for protection from vitamin intoxication because of excessive exposure to sunlight.[4]
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” [4] “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” [4]
1968 Scientific development Hector DeLuca et al. 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.[5]
1968 The idea that vitamin D might function as a steroid-like hormone emerges.[6]
1968–1971 During this period, researchers make great progress in understanding the metabolic processing of vitamin D and its physiological activity.[5]
1969 The vitamin D receptor (VDR) is discovered in the intestine of vitamin D–defi cient chicks.[6]
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”” [4]
1970 Kodicek and Fraser identify renal calcitriol.[5]
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” [4]
1970 Scientific development The hormonal form of vitamin D (calcitriol) is discovered. This would firmly establish the essential role of the kidney in vitamin D biological actions.[4]
1971 Scientific development The chemical structure of metabolite 1,25-dihydroxyvitamin D3 is identified and termed calcitriol.[15][5]
1973 “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” [4]
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” [4]
1974 The existence of a chromosomal receptor for vitamin D is demonstrated.[5]
1974 "The possibility that UV light–catalyzed vitamin D3 synthesis might influence MS susceptibility was proposed in 1974"
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.” [4]
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.[5]
1977 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.[13]
1978 “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” [4]
1970s “Initial studies performed in the early 1970s showed that DHT is efficiently converted to its 25-hydroxylated metabolite” [4]
1980 “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” [4]
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."[8][16] United States
1980 “In 1980 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, Brooke et al” [4]
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” [4]
1980 “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” [4]
1980 “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” [4] “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” [4]
1980 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][17]
1980 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.[1] 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” [4]
1981 “Drawing on ecological studies of variations in cardiovascular disease by season, latitude, and altitude, in 1981 the author published a hypothesis that sunlight and vitamin D may protect against cardiovascular disease” [4]
1981 “The classical consideration of vitamin D as a regulator of calcium and phosphate metabolism and bone biology began to change in 1981, when David Feldman’s and Tatsuo Suda’s groups showed that the most active vitamin D metabolite 1α,25- dihydroxyvitamin D3 (1,25(OH)2D, calcitriol) inhibited the proliferation of melanoma cells and induced the differentiation of leukemic cells” [4]
1981 Reduced vitamin D binding protein levels in people with cystic fibrosis is first reported.[2]
1982 The role of the vitamin D receptor in vitamin D-dependent rickets type-2 is realized.[5]
1983 “In 1983, Sedrani et al. (4) found unexpectedly low vitamin D levels in Saudi university students (n = 59) and in elderly subjects (n = 24), although the mean 25(OH)D levels were significantly lower in elderly subjects (9 nmol/l (3.6 ng/ml)) followed by young males (21 nmol/l (8.4 ng/ml)) and highest in young females (29 nmol/l (11.6 ng/ml))” [4]
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” [4]
1984 Conclusive evidence of the importance of correcting the impaired 25(OH)D availability in chronic kidney disease is reported. [4]
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” [4]
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 hypercalcemia range.[4]
1985 A study reports that of 40 Indonesian patients with active tuberculosis and treated with anti-tuberculosis chemotherapy, 10 patients with the highest Calcifediol levels at the outset of therapy had “less active pulmonary disease”.[2]
1985 “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” [4]
1985 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]
1985 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.[18] Japan (Osaka University)
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” [4]
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” [4]
1986 Colston et al. become the first to demonstrate that 1α,25(OH)2D3 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.[19]
1986 “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” [4]
1986–2000 “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)” [4]
1987 Molecular cloning of the cDNA encoding chick vitamin D receptor is achieved for the first time by McDonnell et al.[5]
1988 The successful cloning of the cDNA encoding the human vitamin D receptor is achieved.[5]
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” [4]
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” [4]
1988 The group of Bert W. O'Malley from California Biotechnology Inc. clones the vitamin D receptor.[5]
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” [4]
1988–2000 “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” [4]
1989 Paricalcitol is patented and approved for medical use.[15]
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” [4]
1989 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.[20][1]
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.[6]
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).” [4]
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” [4]
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” [4]
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” [4]
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” [4]
1990 “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” [4]
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” [4]
1990 Calcipotriol ointment is introduced for the treatment of psoriasis in Denmark.[21] Denmark
1991 Calcipotriol is first approved for medical use.[15]
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” [4]
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."[4]
1992 “In 1992, the first population-based study of the vitamin D status in Saudi Arabia was published” [4]
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” [4]
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” [4]
1993 Tacalcitol ointment is first approved in Japan.[21] Japan
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)” [4]
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."[4]
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)” [4]
1997 Vitamin D5 is first synthesized by researchers at the Department of Chemistry at the University of Chicago.[22]
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]
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” [4]
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” [4]
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.[4] Norway
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” [4]
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” [4]
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” [4]
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.[4] United States
1997 Fu et al. clone 25OHD-1-alpha-hydroxylase.[5]
1998 “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” [4]
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” [4]
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” [4]
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."[2] Wjst and Dold propose that vitamin D supplementation might be the cause of global increases in asthma and allergies.[23]
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"[4]
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” [4]
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.[13]
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 breast cancer.[24][1] United States
2007 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.[25]
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” [4]
2011 (January) Eldecalcitol is approved in Japan, where it is used for the treatment for osteoporosis.[26]
2021 (January 14) 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.[27]

Meta information on the timeline

How the timeline was built

The initial version of the timeline was written by User:Sebastian.

Funding information for this timeline is available.

Feedback and comments

Feedback for the timeline can be provided at the following places:

  • FIXME

What the timeline is still missing

Timeline update strategy

See also

External links

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 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. 3.0 3.1 3.2 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 4.20 4.21 4.22 4.23 4.24 4.25 4.26 4.27 4.28 4.29 4.30 4.31 4.32 4.33 4.34 4.35 4.36 4.37 4.38 4.39 4.40 4.41 4.42 4.43 4.44 4.45 4.46 4.47 4.48 4.49 4.50 4.51 4.52 4.53 4.54 4.55 4.56 4.57 4.58 4.59 4.60 4.61 4.62 4.63 4.64 4.65 4.66 4.67 4.68 4.69 4.70 4.71 4.72 4.73 4.74 4.75 4.76 4.77 4.78 4.79 4.80 4.81 4.82 4.83 4.84 4.85 Holick, Michael F. (23 April 2010). "Vitamin D: Physiology, Molecular Biology, and Clinical Applications". Humana Press. Retrieved 16 August 2021. 
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 Hochberg, Z. (2003). Vitamin D and Rickets. Karger. ISBN 978-3-8055-7582-9. 
  6. 6.0 6.1 6.2 6.3 6.4 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. 
  7. "Vitamin d deficiency: treatments, associated drugs and conditions (21,591 reports) - eHealthMe". www.ehealthme.com. Retrieved 13 September 2021. 
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 Wolf, George (1 October 2004). "The Discovery of Vitamin D: The Contribution of Adolf Windaus". The Journal of Nutrition. 134 (6): 1299–1302. doi:10.1093/jn/134.6.1299. 
  9. "Cod Liver Oil - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 11 August 2021. 
  10. 10.0 10.1 Hochberg, Ze'ev; Hochberg, Irit (15 May 2019). "Evolutionary Perspective in Rickets and Vitamin D". Frontiers in Endocrinology. 10. ISSN 1664-2392. doi:10.3389/fendo.2019.00306. 
  11. 11.0 11.1 "The History and Discovery of Vitamins Through The Ages". What's Up, USANA?. 27 April 2017. Retrieved 14 September 2021. 
  12. Fischer, János; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. ISBN 978-3-527-60749-5. 
  13. 13.0 13.1 13.2 Greer, Frank R. "Issues in establishing vitamin D recommendations for infants and children" (PDF). watermark.silverchair.com. 
  14. DeLuca, Hector F (8 January 2014). "History of the discovery of vitamin D and its active metabolites". BoneKEy Reports. 3. doi:10.1038/bonekey.2013.213. 
  15. 15.0 15.1 15.2 Fischer, János; Ganellin, C. Robin. Analogue-based Drug Discovery. John Wiley & Sons. ISBN 978-3-527-60749-5. 
  16. Holick, M.; MacLaughlin, J.; Clark, M.; Holick, S.; Potts, J.; Anderson, R.; Blank, I.; Parrish, J.; Elias, P (10 October 1980). "Photosynthesis of previtamin D3 in human skin and the physiologic consequences". Science. 210 (4466): 203–205. doi:10.1126/science.6251551. 
  17. 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. 
  18. 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. 
  19. Gombart, Adrian F. (21 November 2012). Vitamin D: Oxidative Stress, Immunity, and Aging. CRC Press. ISBN 978-1-4398-5021-3. 
  20. 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. 
  21. 21.0 21.1 Tarutani, M (October 2004). "[Vitamin D3 for external application--history of development and clinical application].". Clinical calcium. 14 (10): 124–8. PMID 15577144. doi:CliCa041015941598 Check |doi= value (help). 
  22. 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. 
  23. 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. 
  24. 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. 
  25. 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. 
  26. 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. 
  27. "Clinical trial finds vitamin D does not ward off colds and flu". medicalxpress.com. Retrieved 19 March 2021.