Unraveling the Enigma of Vitamin D - Summary

Rickets was a common disease afflicting children in the eighteenth century.
However, the cause for it was not well understood, and many children died because there was no cure (see Tracing the Cause of Disease). As physicians began investigating other diseases such as beriberi, they realized that there were factors in food other than proteins and salts which were essential to health. Research into these “accessory food factors” led scientists to demonstrate the existence of vitamins (see "…a substance different from protein and salts..."). As scientists turned their attention to rickets again, they found that exposure to sunlight seemed to be an effective treatment. Physicians also were attempting to isolate nutrients in food that might help and found that an unknown nutrient in cod liver oil was effective against rickets. Following the designation of vitamins in alphabetic order, they dubbed this new nutrient vitamin D.

Scientists explored the relationship between nutrition and irradiation of foods and found that irradiated foods contained the nutrient that seemed to fight rickets (see Closing in on Rickets). But scientists still knew nothing of what this nutrient was and how it worked to cure rickets. The search continued for the exact substance in food and skin that was activated by ultraviolet radiation. Through extensive research, scientists isolated 3 forms of vitamin D, which made it possible to synthesize the vitamin in large quantities (see Animal, Vegetable or Mineral?). Research continued to determine how vitamin D worked in the body and scientists were able to determine the process by which vitamin D regulates the amount of calcium in the body (see Vitamin D’s Connection to Calcium Control). Further investigations have shown that vitamin D plays many roles beyond maintaining the body’s calcium levels (see More Than Just a Way toRegulate Calcium).

This article is available in German, Spanish and Japanese.

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More Than Just a Way to Regulate Calcium

Now that its role in calcium uptake had been sketched out, researchers in the1970s began investigating vitaminDin greater detail--and with surprising results. Several groups managed to find the vitamin D hormonein the nucleus of cells that were not part of the classical calcium maintenance system including the brain, lymphocytes (infection fighting white blood cells), skin, and malignant tissues. What business would vitamin D have in these places?

In the early 1980s, Japanese researcher Tatsuo Suda made the exciting discovery that adding the hormone to immature malignant leukemia cells caused the cells to differentiate, mature, and stop growing. The amount of vitamin D hormone needed to stop the runaway growth of tumors and cancers has so far proved too toxic for human use, but Suda's discovery suggested that this fascinating hormone had roles beyond the part it played in maintaining the body's calcium levels. This finding spurred on a new era in vitamin D research.

In the mid 1980s, a group of researchers led by S. C. Manolagas found that vitamin D hormone also seemed to play a part in modulating the immune system. In 1993, S. Yang and other researchers in DeLuca's laboratory found that rats given a large dose of vitamin D hormone were protected from the inflammation normally associated with wounds and chemical irritants. This unexpected immunosuppressantfunction for vitamin D hormone suggested a whole new range of possibilities--including its use in the control of autoimmune diseases.

More developed is vitamin D hormone's effect on psoriasis, a disfiguring skin disorder that affects some 50 million people worldwide. For reasons unknown, psoriasis causes skin cells to multiply uncontrollably. Failing to differentiate and develop normally, the skin cells clump in unsightly rashes, scales, and scars. In the 1980s, a Japanese research team demonstrated that 1,25-dihydroxyvitamin D3 can inhibit skin cell growth. A team of scientists at Boston University School of Medicine, led by Michael F. Holick, investigated this inhibition further and reasoned that it could be used for the treatment of psoriasis.

Initial experiments by Holick and coworkers with vitamin D hormone have shown that topical applications of the hormone are remarkably effective. After two months, the lesions of 96.5 percent of the patients treated with a topical calcitriol (vitamin D hormone) preparation had improved with no noticeable side effects, as compared with 15.5 percent of the controls treated with petroleum alone. In 1994 the U.S. Food and Drug Administration approved a vitamin D--based topical treatment for psoriasis, called calcipotriol.

As we enter the twenty-first century, we recognize that the basic scientific research done in the previous two centuries has not only untangled the workings of the elusive vitamin D hormone, but also and has given us ways to protect the health of both adults and children. Researchers are pursuing many new applications for vitamin D, but its
role in building and maintaining bone continues to be an important health issue, especially among middle-aged and older adults.
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Tracing the Cause of Disease

The first solid hint that a specific dietary deficiency could lead to disease came in 1754. In that year the Scottish naval surgeon James Lind showed that scurvy--the painful and sometimes fatal bane of mariners on long ocean voyages--could not only be cured but also prevented with the juice of oranges, lemons, and limes. By the late eighteenth century, British sailors (soon nicknamed "Limeys") were reaping the benefit of Lind's discovery.

Meanwhile, the advent of the Industrial Revolution in Britain in the late 1700s brought with it a different scourge: rickets. The disease itself had first been described by physicians in the mid 1600s, but it was then relatively rare. By the nineteenth century, however, as more and more families left the outdoor life of the farm for factory work in the smoggy air of industrial cities, rickets had become a plague all over Europe. Symptoms of the disease were unmistakable. The bones of afflicted infants remained soft, like cartilage, and the babies were slow to sit, crawl, and walk. As the children grew, their soft bones bent under the additional weight, leaving the children with rickets' telltale pigeon breast, bowed legs, or knock-knees. Rachitic children (that is, children with rickets) also suffered from tetany: painful spasms of the hands, feet, and larynx, along with difficulty in breathing, nausea, and convulsions. This condition, later found to be symptomatic of insufficient calcium, was often so severe that children died.

Throughout the nineteenth century, sporadic reports of cures for rickets surfaced, but with little effect. In 1822, for example, a Polish physician observed that children in Warsaw suffered severely from rickets, whereas the disease was virtually unknown in the city's rural outskirts. After experimenting with the two groups, he concluded that sunbathing cured rickets. Five years later, a French researcher reported cures among those given the home remedy cod-liver oil. Neither treatment gained widespread attention, in part because the prevailing medical wisdom was that people needed only to get adequate amounts of the so-called macronutrients--proteins, fats, and carbohydrates--in order to maintain health. However, researchers looking into the causes of such diseases as pellagra and beriberi began to suspect that the macronutrients might not be the whole story--that, in fact, there was more to ordinary food than met the eye.

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Glossary

autoimmune diseases Diseases, such as lupus, in which the immune system attacks native elements of the body.

beriberi A vitamin deficiency disease, caused by a lack of vitamin B1. Symptoms include irritability and fatigue, and later, numbness in the extremities, seizures and decreased mental ability.

calcify To harden by the deposit of calcium. Too much calcium in the body causes organs to calcify and cease to function.

cartilage Tough elastic tissue such as that found in the joints, outer ear, and nose.

hormone A chemical produced by one part of the body that causes or regulates a biological action in another part of the body.

immunosuppressant An agent that lowers the body's normal immune response.

irradiation The process of exposing something to radiation. Irradiation is used to sterilize foods and to provide cancer therapy.

metabolic pathway The process by which a substance is transformed into a succession of new substances after reacting with enzymes.

metabolite Any substance involved in metabolism, either as a product of metabolism or as a necessary component.

multiple sclerosis A disorder of the central nervous system (brain and spinal cord) involving decreased nerve function associated with the formation of scars on the covering of nerve cells. There are many symptoms, which include numbness or pain in the extremities, vision problems, and speech problems.

pellagra A disease caused by a deficient diet or failure of the body to absorb niacin. The disease is characterized by scaly skin sores, diarrhea, mucosal changes, and mental symptoms. Pellagra may develop after gastrointestinal diseases or alcoholism.

psoriasis A chronic skin disease characterized by red patches covered in white scales.

rickets A disease characterized especially by soft and deformed bones. Rickets is caused by the body's failure to use calcium and phosphorus normally due to inadequate sunlight or vitamin D. Rickets primarily affects the young.

scurvy A disease caused by a lack of vitamin C. Symptoms include bleeding and spongy gums, bleeding from mucous membranes, paleness, depression, and general weakness.

vitamin A A family of fat-soluble vitamins that promote healthy skin and teeth and good vision. Retinol is one of the most active, or usable, forms of vitamin A. A deficiency in vitamin A can cause problems including night blindness, and dry skin. Vitamin A can be found in foods like egg yolks, milk, butter, yellow and orange vegetables, and fish-liver oils.

vitamin C A water-soluble vitamin that promotes healthy teeth and gums, helps in the absorption of iron, aids in the maintenance of normal connective tissue, and promotes wound healing. Vitamin C also helps the body's immune system. A deficiency in vitamin C can cause scurvy. Vitamin C can be found in citrus fruits and many vegetables.

vitamin D A fat-soluble vitamin that promotes the body's absorption of calcium, which is essential for the normal development of healthy teeth and bones.

Vitamin D also helps maintain adequate blood levels of the minerals calcium and phosphorus. A deficiency in vitamin D can lead to rickets. Vitamin D is found in dairy products, fish, and oysters.

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Vitamin D is present in many parts of the body

The discovery that Vitamin D is present in the nuclei of cells in many different tissues of the body has led scientists to begin exploring a variety of new applications, further revealing the potential benefits of this once enigmatic hormone