Discovery and Characterization of Vitamin D: A Milestone in Nutritional Science

The early 20th century marked a pivotal period in the understanding of vitamins, particularly the discovery and characterization of vitamin D. The groundwork for this discovery was laid by Sir Edward Mellanby in 1919/20 when he conducted groundbreaking experiments to investigate the cause of rickets, a bone disease that was prevalent at the time. Mellanby’s work involved raising dogs in an environment devoid of sunlight or ultraviolet light, thereby mimicking conditions that could lead to rickets. He meticulously devised a diet that allowed him to determine that rickets was indeed caused by a deficiency of a trace component in the diet. This crucial finding was a significant step forward in understanding the role of nutrition in preventing disease.

In 1921, Mellanby published his findings, stating, "The action of fats in rickets is due to a vitamin or accessory food factor which they contain, probably identical with the fat-soluble vitamin." This statement was revolutionary, as it suggested that rickets could be prevented by a dietary component found in certain fats, particularly cod liver oil. Mellanby’s identification of cod liver oil as an excellent antirachitic agent was a milestone in nutritional science, as it provided a practical means of preventing rickets through dietary supplementation.

Mellanby’s work laid the foundation for further research into the fat-soluble vitamins. Shortly after Mellanby’s discovery, E.V. McCollum and his associates conducted experiments that distinguished between two fat-soluble vitamins, vitamin A and vitamin D. By bubbling oxygen through a preparation of the "fat-soluble vitamin," they observed that vitamin A was inactivated, whereas vitamin D retained its activity. This distinction was critical in understanding the specific roles of these vitamins in human health.

The identification of the role of sunlight in vitamin D production came soon after. In 1923, Goldblatt and Soames made a breakthrough discovery when they identified that 7-dehydrocholesterol, a precursor of vitamin D found in the skin, could be converted into an active form of vitamin D when exposed to sunlight or ultraviolet light. This finding provided a biological explanation for the protective effect of sunlight against rickets, further cementing the connection between sunlight exposure and vitamin D synthesis.

Hess and Weinstock later confirmed this connection through an innovative experiment. They excised small portions of skin from rats, irradiated the skin with ultraviolet light, and then fed it to groups of rachitic rats. The irradiated skin provided absolute protection against rickets, while the unirradiated skin did not, conclusively demonstrating that irradiated skin could produce sufficient quantities of vitamin D to prevent rickets. This experiment also suggested that vitamin D might not be an essential dietary trace constituent, as it could be synthesized in the body through exposure to light.

In parallel studies, Steenbock and Black discovered that food irradiated with ultraviolet light also acquired antirachitic properties. This finding underscored the importance of vitamin D in preventing rickets and further solidified its classification as a vitamin. The rapid advances in nutritional science during this period, particularly the identification of water-soluble and fat-soluble vitamins, played a crucial role in establishing vitamin D as a key nutrient necessary for bone health and the prevention of rickets.
Discovery and Characterization of Vitamin D: A Milestone in Nutritional Science

The first scientific description of a vitamin D-deficiency by Dr. Daniel Whistler

The term ‘rickets’ first appeared in 1634 when listed as a cause of death in London’s Annual Bill of Mortality.

The first scientific description of a vitamin D-deficiency, namely rickets, was provided in the 17th century by both Dr. Daniel Whistler and Professor Francis Glisson.

It was that English physician Dr. Daniel Whistler described its symptoms in 1645. The publication by Whisker was a concise monograph of only 14 pages and was written when author was 26 years old. It represented the thesis required for his degree of doctor of medicine. His thesis was ‘De morbo perili Anglorum’ - The Children’s disease of the English.

The Latin thesis was read at Leiden on 18th October 1645. The importance of this thesis lies in the fact that it contained the first complete clinical account of rickets. Whistler's book was published a short time after the reading of his thesis in 1645. It was a small quarto volume of some eighteen pages, though when it was reprinted in 1684, it was in octavo.

In his thesis Dr. Whistler proposed a wide range of suggestions for treatment from crow’s or frog’s livers, application of leeches, purgation, poultices of snails and salt placed on the belly, and grease from mainly pork fat, goosegrease and butter to be smeared on the swollen epiphyses.
The first scientific description of a vitamin D-deficiency by Dr. Daniel Whistler

Edward Mellanby and study of rickets

Rickets in young children, known for centuries as the English disease, was fully described in 1650 by Francis Glisson, Regius Professor of Physic at Cambridge, and also four years earlier in a thesis presented to the University of Leyden by Daniel Whistler, a medical student from Oxford. Whistler published a monograph titled “Inaugural medical disputation on the disease of English children which is popularly termed the rickets.”

Whistler provided a succinct description of the signs and symptoms of rickets in his thesis and used an alternate term called “Paedosteocaces” to describe the clinical symptoms of rickets.

It was in 1919/20 that Sir Edward Mellanby, an English physician, working with dogs raised exclusively indoors (in the absence of sunlight or ultraviolet light), devised a diet that allowed him to unequivocally establish that the bone disease, rickets was caused by a deficiency of a trace component present in the diet.

Vegetable oils such as olive oil, cotton seed oil and linseed oil permitted development of rickets, where as it could be prevented or cured with cod liver oil or egg yolk. Mellanby concluded that a vitamin substance preventing rickets was present in these fats.

In 1921 he wrote, "The action of fats in rickets is due to a vitamin or accessory food factor which they contain, probably identical with the fat-soluble vitamin." Furthermore, he established that cod liver oil was an excellent antirachitic agent.

Mellanby had presumed that calcium and phosphorus were adequate in all of his rachitic diets but it was soon established that all of his diets were relatively deficient in calcium and lacked favorable calcium phosphorus ratios. Mellanby’s work clearly established the role of diet in the cause of rickets.
Edward Mellanby and study of rickets

Disease of growing bone: Rickets

Rickets is a disease that affects bone structure, resulting in soft and weakened bones and is particularly damaging to the weight-bearing bones in the legs, spine, and pelvis. A similar disease process occurs in adults and is known as osteomalacia, or simply soft bones.

It is characterized by malformed and weak bones because of poor calcium and phosphorous deposition.

Rickets is more likely to occur in children eating a poor diet and living in northern countries, where there is less sunshine. Vitamin D allows the body to absorb calcium from food and makes sure that the calcium is passed from the blood into the bone when the bone is being formed.

Defective mineralization of both bones and cartilaginous material in the epiphyseal growth plate becomes apparent as the child grows.

In rare cases, there may be rickets of urinary origin, where there are excessive urinary losses of either calcium or phosphorus. Vitamin D-resistant rickets is, in most cases, a genetic disorder where excessive phosphate is lost in the urine which reduces the supply available for mineralization of bone.

Rickets was first identified in Europe in the 1600s when the lack of sunlight and meager, unbalanced diet available to working class city dwellers cause an epidemic of rickets until the early 1900s.

Disease of growing bone: Rickets

Modern History of Rickets

The rickets were first know in the West of England, in the counties of Dorset and Somerset.

The rickets appeared first about the year 1620 an afterwards travel into all parts of England. It is an old disease that became epidemic after 1650 when soft coal was introduced as a fuel source.

The origin of the term is uncertain. Suggestion have included English racket – short of breath, and rucken – to rock or reel.

The term ‘rickety’ came to mean ‘shaky or tottering’ because the person so afflicted were impaired in posture and gait.

Rickets might be an Anglicized corruption of the Greek rhachitis, or it might have originated in the Old English ‘wricken’, ‘to twist’.

Whatever origin, the word ‘rickets’; first appears in a Bill of Mortality for 1634 as accounting for fourteen death, the number from that cause increasing year by year until 1659 when surprising figure of 476 out of less than 15,000 burials or 3% of total deaths is recorded.

The first full description of the disease was written in the seventeenth century by the English physician Glisson.

While rickets has a distinguished antiquity, historically, it came to medical attention particularly in the seventeenth and eighteenth centuries in Europe, not appearing in the U.S.A until the latter part of the nineteenth century.

In 1822, a Polish physician observed that children in Warsaw suffered severely from rickets, yet rickets was unheard outside of the city, he concluded that sunbathing was the cure for rickets.

Huldschinsky, in 1919, was the first to prove that exposure of the skin to ultraviolet radiation could cure rickets.

Within two years, Hess and Unger reported that exposure of several rachitic children to sunlight was adequate for curing this bone deforming disease.
Modern History of Rickets

Vitamin D deficiency can cause rickets

In an infant or child this deficiency results in the disease called rickets, in which the rapidly growing bones grow soft and eventually bend under the weight of the body.

It’s a defect in the mineralization of bone matrix with increase bone mass.

Affected children lack the exposure to ultraviolet light necessary for the dermal synthesis of vitamin D and have a poor diet in vitamin D in which the component (high fiber and high cereal) probably contribute to the excessive breakdown of vitamin D.

In adults, the same disorder is called osteomalacia or adult rickets. It is to be distinguished from osteoporosis where bone mass is decreased from hypophosphatemic osteopeniaof premature infants, and from renal osteodystrophy.

The name rickets is from the Old English wrickken, to twist. The more technical medical term, rachitis, which comes from Greek, the spine , was suggested by Francis Glisson in 1650.

Vitamin D deficiency rickets occurs in underprivileged populations throughout the world, particular in the northern hemisphere.

Women in United States usually take multivitamins and eat vitamin D dairy foods so rickets and vitamin D deficiency is less a problem than in developing countries and northern Europe.
Vitamin D deficiency can cause rickets