Vitamin D: part II; cod liver oil, ultraviolet radiation, and eradication of rickets.

PURPOSE: After Glisson's description of rickets, it took two centuries to realize that rickets was due to the absence of antirachitic nutrients in the diet or lack exposure of the skin to ultraviolet rays. This bone disease caused by vitamin D deficiency was one of the most common diseases of children 100 years ago. This paper explores how the definition, diagnosis, and treatment of rickets shifted in the first decades of the twentieth century. MATERIAL AND METHODS: Although benefits of cod liver oil as food were known as early as the seventh century, cod liver oil was only proposed as medicinal for rickets in Northern Europe at the end of the eighteenth century. The relationship between rickets and nutritional deficiency was suspected and demonstrated between 1880 and 1915, at the same time of the discovery of other vital substances (vitamins) needed to prevent beriberi, scurvy, and pellagra. Understanding that the lack of photosynthesized vitamin D or the lack of dietary vitamin D was a similar risk of rickets was an important turn in the comprehension of the disease. We look at the sequence and turn of events related to the discovery of vitamin D. RESULTS: Rickets has been recognized first as a disease of urban living people. Cod liver oil had been used since 1700 as a nonspecific treatment for a range of diseases. Generations of children in cities of the north of Europe had learned to hate the taste and smell of the black oily liquid and then grown up to be parents who, in turn, hated to force it down their children's throats. Occasional papers before 1900 pointed to its efficacy for rickets, and most textbooks of the early 1900s mentioned it only as a treatment option. The discovery in the early 1900s that artificial and natural ultraviolet rays had both antirachitic activity allowed to produce antirachitic foods just by food irradiation with artificial ultraviolet irradiation. Clinical guidelines were adopted to propose exposure to sunlight or to artificial ultraviolet radiation to prevent rickets in children. By the mid-1920s, rickets was promoted as universal, at times invisible to non-experts, but present to some degree in nearly every young child regardless of race or class. It was thus used to promote the young disciplines of preventive medicine, pediatrics, and public health. Innovative advances were made in the understanding of vitamin D synthesis from 1915 to 1935. A public health campaign of the 1930s was a success to eradicate rickets, using irradiated ergosterol from yeast to enrich milk and other foods with vitamin D, ensuring that the general population was consuming sufficient vitamin D. CONCLUSION: Rickets therefore provides an excellent window into the early politics of preventive health and the promotion of targeted interventions in the world. It is also a relevant historical counterpoint for current debates over the role of risk factors (absence of light or sun) for disease (today's so-called "lifestyle" diseases).

Analysis of patterning in the occurrence of skeletal lesions used as indicators of vitamin D deficiency in subadult and adult skeletal remains.

Paleopathological investigations of conditions linked to vitamin D deficiency have increased in the last twenty years, and a suite of skeletal lesions has been established to aid in the diagnosis of vitamin D deficiency disease in subadults and adults. This paper analyzes the occurrence of these lesions in a large skeletal series comprising 3541 Roman period individuals (1st-6th century AD). Sixteen lesions reported in rickets in subadults, and 13 associated with residual rickets and osteomalacia in adults, were analyzed. Among subadults, there were clear associations among post-cranial lesions. Porotic cranial changes were associated with each other, but not with post-cranial lesions. A range of conditions could have produced the cranial lesions. There was a general paucity of correlations between indicators found in adults, and the difficulty in recording bending deformities was clear. Pseudofractures appear to provide a useful means of investigating osteomalacia in adults. In general, a simple algorithmic approach using presence or absence of lesions is unlikely to provide an adequate means of diagnosing vitamin D deficiency in paleopathology. Knowledge and consideration of the underlying physiological mechanisms involved in lesion formation, combined with individual judgement, will be required to differentially diagnose cases.

Gender-related vitamin D deficiency in a Dutch 19th century farming community.

The most common cause of vitamin D deficiency is inadequate dermal exposure to sunlight. Residual rickets is nonadult vitamin D deficiency still evident in an adult individual, whereas osteomalacia occurs in adulthood. Previous research on the Beemster population, a 19th century rural community in the Netherlands, identified rickets in 30.4% of the nonadults between the ages of two and four years (n=7/23). Because the sex of these nonadults was not known it was not possible to determine if there were differences between boys and girls. To overcome this gap in our knowledge, the aim of this paper is to determine if there are gender related differences in vitamin D deficiency in the Beemster skeletal collection, based on adults with residual rickets and osteomalacia. Out of 200 adults (100 females; 100 males) no cases of osteomalacia were detected. However, there were 29 cases of residual rickets (14.5%), with 21 of those cases in females (21.0%; 21/100). A complex interplay of multiple factors is proposed to have affected vitamin D levels in nonadults, including sociocultural variables such as gender-based labour norms. This research highlights the importance of continuing to explore gender-based health differences in past populations.

Rare paleopathological insights into vitamin D deficiency rickets, co-occurring illnesses, and documented cause of death in mid-19th century London, UK.

Growing evidence suggests that vitamin D supports immune responses to infections, autoimmune conditions and cancers, although evidence from large-scale studies is limited. There is scope to better understand how vitamin D deficiency interacted with other diseases to affect health in past groups. This study investigated paleopathological evidence and documentary records of individual cause of death to examine disease co-occurrence in a group of mid-19th century child burials from London, UK. Twenty-one percent of children had vitamin D deficiency rickets (138/642) and 36 children with rickets had an identified cause of death. Cyclical episodes of metabolic and nutritional deficiencies (rickets and scurvy) had occurred during childhood. Active rickets co-occurred with respiratory and gastrointestinal infections in a small number of children, likely reflecting vitamin D's role in supporting immune function. Consideration of the stage of the vitamin D deficiency showed that the majority of children were affected by chronic disease loads indicative of multiple episodes of illness. Reconstructions of the wider health consequences of vitamin D deficiency in past groups are dependent on recognising whether the deficiency was active or healed. The variability of diseases identified illustrates the high disease burden that affected children in this socially disadvantaged group.

The discovery and synthesis of the nutritional factor vitamin D.

Although vitamin D deficiency was first recognized as rickets/osteomalacia in the early 1600s, it was only a century ago that vitamin D, the nutritional factor responsible, was discovered. This discovery was made difficult by the fact that the substance could be synthesized in human skin by exposure to UV light and could also be present in the diet in animal-derived (D3) and plant-derived forms (D2). Prior to 1920, the frequency of vitamin D deficiency in the general population of industrialized cities was high. The discovery of vitamin D led to the widespread fortification of foods e.g. milk and the virtual eradication of rickets in developed nations. Vitamin D3 was first chemically synthesized in the 1930s and its metabolism to the active form 1,25-dihydroxyvitamin D3 and its mode of action in calcium and phosphate homeostasis were elucidated in the latter half of the 20th century. Synthetic vitamin D analogs that mimic the physiological effects of vitamin D are now used therapeutically in diseases such as bone disease, chronic kidney disease and psoriasis. Thus, a wide range of disciplines played critical roles in the rich history of vitamin D and these are described in this short historical overview.

Medical diagnostic methods applied to a medieval female with vitamin D deficiency from the north of Spain.

Vitamin D deficiency is a pathological condition that affects bone metabolism by preventing proper mineralization, which eventually leads to bone deformities and other pathological conditions such as osteoporosis, increased bone fragility and fractures. The aim of this study is to present a case of vitamin D deficiency, but also to note how the application of several complementary techniques is a fundamental step in the establishing an accurate diagnosis. These techniques range from classical palaeopathological analysis to modern clinical practice. After the macroscopic examination of a medieval female skeleton from Palencia (Spain), where various bone deformations were observed, a differential diagnosis could not establish a definitive cause. Radiological, bone density, and histological studies were carried out, finally allowing to confirm a vitamin D deficiency suffered in both childhood and adulthood. This is a clear example, with practical applications, of the importance of interdisciplinarity to reveal insights about the life history and physical health of ancient individuals.

Latitude, urbanization, age, and sex as risk factors for vitamin D deficiency disease in the Roman Empire.

OBJECTIVES: The aims of the study are to investigate the effects of latitude, settlement type, age, and sex on the prevalence of vitamin D deficiency disease in the Roman Empire using human skeletal remains from cemetery sites (1st to 6th cent. AD). MATERIALS AND METHODS: Data from 2,787 individuals (1,143 subadults, 1,644 adults) from 18 cemeteries associated with 15 different settlements in the Mediterranean and north-western Europe were analyzed. Vitamin D deficiency disease (rickets, osteomalacia) was identified using standard paleopathological criteria. Multivariate statistical analysis was used analyze the effects of the variables of interest on the prevalence of vitamin D deficiency. RESULTS: The overall prevalence of rickets in subadults (<20 years) was 5.7%, and 3.2% of adults showed osteomalacia and/or residual rickets. There was a positive association between rickets in subadults and latitude, with numerous cases of rickets among infants. There was no general association with sex or settlement type, although an elevated prevalence of rickets was observed at a cemetery associated with a settlement (Ostia, Italy), which had multi-storey buildings. DISCUSSION: The association of rickets with latitude may reflect care practices that, in more northerly locations where solar radiation is less intense, placed infants at increased risk of insufficient sunlight exposure to permit adequate vitamin D biosynthesis. The elevated level of vitamin D deficiency at Ostia may reflect, at least in part, the lack of sunlight due to dense occupation of multi-storey blocks that prevented direct sunlight from reaching living quarters and the streets between these closely spaced buildings.

The pathology of vitamin D deficiency in domesticated animals: An evolutionary and comparative overview.

Although vitamin D is critical to calcium/phosphorus homeostasis, bone formation and remodeling, there is evolution-based variation between species in vitamin D metabolism and susceptibility to rickets and osteomalacia. Most herbivores produce vitamin D3 in response to sunlight, but dogs and cats have generally lost the ability as carnivore diets are rich in vitamin D. Nutritional deficiencies and/or poor exposure to sunlight can induce rickets in birds, swine, cattle and sheep, but horses are less susceptible as they have evolved a calcium homeostasis that is quite different than other animals. Adaptations to specific environments also affect disease incidence: llamas/alpacas out of their natural high altitude intense solar radiation environments are highly susceptible to vitamin D deficiency. The pathology of rickets/osteomalacia is similar across species, however fibrous osteodystrophy is more common and may also be present. Rickets/osteomalacia were likely more common in animals before the advent of commercial diets, but can be difficult to definitively diagnose especially in single archeological specimens. Consideration of species susceptibility, location - especially in terms of latitude, and any available information on diet, season of occurrence, husbandry practices or descriptions of affected animals can support the diagnosis of metabolic bone disease in animals.

[Brief history of rickets and of the discovery of vitamin D]. / Breve história do raquitismo e da descoberta da vitamina D.

Almost eighteen centuries mediated between the first cases of rickets, reported by Soranus and Galeno, and the clarification of the disease aetiology. Due to the outbreak of rickets verified in the 17th century in England, the situation was known as the 'English disease', being its first detailed description presented by Francis Glisson. The growing incidence of rickets with the Industrial Revolution raised speculations about its origin and treatment. The characterization of solar light and luminous spectrum led to the identification of the biological effects of ultraviolet radiation, and to the discovery of phototherapy as an alternative therapeutic process to the solar irradiation. The experimental rickets achieved by Mellanby and McCollum gave support to the concept that this situation could have an origin in a dietary defect. It was also referred an inverse relationship between sun exposure and the incidence of rickets. The identification of the chemical nature of an essential dietary factor with anti-rickets effect (ergocalciferol or vitamin D2), together with another factor with identical properties, but more potent, produced in the skin exposed to sunlight (cholecalciferol or vitamin D3), was essential to the elucidation, prevention and therapy of the disease. The present revision summarizes the history of rickets, the characterization and anti-rickets properties of the light and dietary supplements of lipid nature, and the identification of the major biological forms of vitamin D.

Fortification of industrialized foods with vitamins

Vitaminas são nutrientes essenciais à vida. Hábitos alimentares inadequados, alto consumo energético e falhas no metabolismo levam a deficiências de micronutrientes, que afetam mais de dois bilhões de pessoas mundialmente. O consumo, cada vez maior, de alimentos industrializados, somado à baixa estabilidade das vitaminas, têm induzido à prática de adição de nutrientes aos alimentos processados. Esta revisão discute terminologia, disponibilidade, ingestão e risco de hipervitaminose devida ao consumo desses produtos, e a importância nutricional dos de alimentos fortificados com vitaminas. A adição de nutrientes deve ocorrer em alimentos que, efetivamente, participem da dieta da população alvo e deve obedecer às necessidades reais de segmentos significativos da população. No Brasil, se encontra, disponível em supermercados, um total de 166 produtos enriquecidos com vitaminas. Um estudo de coorte de 10 anos, desenvolvido na Alemanha, com crianças e adolescentes, comprovou que 90% dos pesquisados utilizaram, pelo menos, um alimento fortificado. Ao longo do período estudado, observou-se o consumo de 472 diferentes produtos fortificados. O enriquecimento de alimentos, entretanto, deveria basear-se nas necessidade de cada país, e, se possível, nas necessidades regionais, que variam de região a região. Na Dinamarca, por exemplo, durante o inverno, e principalmente nos idosos, a vitamina D necessita ser adicionada aos alimentos, para que aumente o seu consumo. No Brasil, diferentemente, não há evidências de necessidade de fortificação de alimentos com essa vitamina. Apesar disso, uma investigação mostrou que, de 76 produtos lácteos enriquecidos, 37 continham vitamina D. A fortificação de alimentos é uma estratégia importante para resolver problemas de deficiência nutricional, porém também pode ocasionar muitos danos à saúde.