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).

Early animal models of rickets and proof of a nutritional deficiency hypothesis.

In the period between 1880 and 1930, the role of nutrition and nutritional deficiency as a cause of rickets was established based upon the results from 6 animal models of rickets. This greatly prevalent condition (60%-90% in some locales) in children of the industrialized world was an important clinical research topic. What had to be reconciled was that rickets was associated with infections, crowding, and living in northern latitudes, and cod liver oil was observed to prevent or cure the disease. Several brilliant insights opened up a new pathway to discovery using animal models of rickets. Studies in lion cubs, dogs, and rats showed the importance of cod liver oil and an antirachitic substance later termed vitamin D. They showed that fats in the diet were required, that vitamin D had a secosteroid structure and was different from vitamin A, and that ultraviolet irradiation could prevent or cure rickets. Several of these experiments had elements of serendipity in that certain dietary components and the presence or absence of sunshine or ultraviolet irradiation could critically change the course of rickets. Nonetheless, at the end of these studies, a nutritional deficiency of vitamin D resulting from a poor diet or lack of adequate sunshine was firmly established as a cause of rickets.

[Radiated drugs, the way of health]. / Médicaments irradiés, sources de santé.

During the inter-war years, the word "radiated" did not only suggest radioactivity, but it was also used to indicate exposure to others radiations, such as ultraviolets. The actinotherapy, a new therapy in vogue, was applied to many pathologies and tried on many substances. "Radiated drugs" result of those experimentations. Their therapeutical characteristics were found during searches on rickets. Our study relates the story of fight against rickets in France, from the use of cod liver oil to the synthesis of Vitamine D.

[Omega-3: from cod-liver oil to nutrigenomics]. / Omega-3: dall'olio di fegato di merluzzo alla nutrigenomica.

The leading role of cod-liver oil on rickets was a relevant factor in the knowledge of this disease. In 1922 the preventive and therapeutic value of cod-liver oil and sunlight against rickets in young infants was confirmed. The seasonal variation in the incidence of rickets, the role of skin pigmentation, of diet and the fact that breast milk was not an adequate source of vitamin D were understood. The discovery of essential fatty acids omega-6 and omega-3 have shown that deficiencies, mainly of omega-3 long chain polyunsaturated fatty acids, result in visual and cognitive impairment and disturbances in mental functions in infants and also in cognitive function in adults, as fatty acids are beneficial to vascular health and may forestall cerebrovascular disease and thus dementia. An adequate ratio of n-6 and n-3 fatty acids may promote a healthier balance of eicosanoids, which would protect membrane function with a nutraceutical function. Dietary lipids not only influence the biophysical state of the cell membranes but, via direct and indirect routes, they also act on multiple pathways including signalling, gene and protein activities, protein modifications and they probably play important role in modulating protein aggregation. Significant advances have been made in understanding the relation between dietary factors and inflammation, which is a central component of many chronic diseases, including coronary artery disease, rheumatoid arthritis, cancer prevention. However, the identification of those who will or will not benefit from dietary intervention strategies remains a major obstacle. Adequate knowledge about how the responses depend on an individual's genetic background (nutrigenetic effects), the cumulative effects of food components on genetic expression profiles through nutrigenomics mechanism, may assist in identifying responders and non-responders. Thus, fish and fish oil consumption might encourage brain development and gene expression to brain maintenance during aging through nutrigenomic mechanism.

Reemerging nutritional rickets: a historical perspective.

Recent case reports highlight the resurgence of rickets in certain groups of breastfed infants. Infants residing in the North, irrespective of skin color, and dark-skinned African American infants residing anywhere in the United States are most vulnerable to nutritional rickets if they are exclusively breastfed past age 6 months without vitamin D supplementation. At the turn of the 20th century, rickets was nearly universal among African American infants living in the North. The discovery of vitamin D, the initiation of public health campaigns to fortify infant foods with vitamin D, and the supplementation of vitamin D to breastfed infants were responsible for overcoming the rickets scourge. We review a classic nutritional study by Alfred F. Hess, one of the greatest clinical nutritional researchers of the early 20th century, in the context of the resurgence of rickets, especially among dark-skinned infants. The Columbus Hill district, a black community of New York, NY, served as the setting for the study. Sixty-five infants (aged 1-17 months) entered a 6-month open-label trial of daily cod liver oil therapy. Participants were assessed for signs of rickets at recruitment and at 2, 4, and 6 months. Cod liver oil prevented the development of rickets in 34 (92%) of 37 infants treated for 6 months and in 7 (58%) of 12 treated for 4 months. Of the 16 infants who did not take the prescribed treatment, rickets progressed unremittingly in 15. Hess translated his success into a public health campaign leading to the development of the first rickets clinic in 1917. This was the first step in the conquest of the rickets epidemic of the early 20th century.

Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective.

Rickets, a disease of vitamin D deficiency, is rarely confronted by the practicing pediatrician in the United States today. At the turn of the 20th century, rickets was rampant among the poor children living in the industrialized and polluted northern cities of the United States. With the discovery of vitamin D and the delineation of the anti-rachitic properties of cod-liver oil by the 1930s, it became possible to not only treat but also eradicate rickets in the United States. Rickets was a common disease in 17th century England. Frances Glisson's treatise on rickets published in 1650, a glorious contribution to English medicine, described the clinical and anatomic features of rickets in great detail. The exact etiology of rickets had been elusive until the 1920s. During the Glissonian era, rickets was a mysterious disease. By the late 19th and early 20th century, faulty diet or faulty environment (poor hygiene, lack of fresh air and sunshine) or lack of exercise was implicated in its etiology. Animal experiments, appreciation of folklore advocating the benefits of cod-liver oil, and the geographical association of rickets to lack of sunshine were all relevant factors in the advancement of knowledge in the conquest of this malady. In this article, the history of rickets pertaining to the discovery of vitamin D, cod-liver oil, and sunlight is reviewed.

Cod-liver oil, vitamin D and the fight against rickets.

Although rickets has all but disappeared as a medical problem, the disease caused serious concern in turn-of-the-century England, where it reached epidemic proportions. The connection between rickets and a lack of vitamin D wasn't made until shortly after World War I, when it was determined that regular exposure to sunlight would eliminate the problem; another solution was to provide vitamin D supplements in milk. The problem hasn't disappeared entirely, however. Seventeen cases of rickets have been diagnosed at Toronto's Hospital for Sick Children in the past 5 years.