The health benefits of vitamin D has been long been known in medical and scientific literature but few studies have been devoted for the ultimate causation of why humans need vitamin D. However, this has changed as deeper investigation has been done in recent years. Contemporary research has shown how vitamin D's biological mechanism in the body has been specifically selected during millions of years of evolution and indicates that vitamin D plays a more significant role in human health than previously thought. One hypothesis even suggests that vitamin D helps protect against influenza. In addition, research has shown that vitamin D may provide protection from osteoporosis, hypertension (high blood pressure), cancer, and several autoimmune diseases. New knowledge about the health effects of the "sunshine vitamin" is very likely to play a major role in the treatment and prevention of a wide range of diseases.
Vitamin D is a fat-soluble vitamin that is naturally present in very few foods. Because of this, it is often added to products such as fortifying milk and is available as a dietary supplement. The two major forms are vitamin D2, also known as ergocalciferol, and vitamin D3 or cholecalciferol. Vitamin D3 is also produced naturally in the human body when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis (Holick, 2003). Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first step occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second step occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol (Vitamin D Factsheet).
In the human body, vitamin D aids in the absorption of calcium, helping to form and maintain strong bones. It does this by maintaining normal blood levels of calcium and phosphorus. This enables normal mineralization of bone and prevents hypocalcemic tetany. (DeLuca, 2008). Vitamin D is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D deficiency results in rickets in children and osteomalacia in adults. Together with calcium, vitamin D also helps protect older adults from osteoporosis (Vitamin D Factsheet). Vitamin D deficiency is also linked to increased risk of chronic diseases including type I diabetes, rheumatoid arthritis, Crohn's disease, multiple sclerosis, heart disease, and stroke as well as increased risk of dying from cancers of the colon, prostate, and breast (Holick, 2009).
Though the full details on how this process initially occurred remains a mystery, it is known that the photosynthesis of vitamin D evolved over 750 million years ago. At this time, the phytoplankton Emeliani huxleii was an organism that lived in the Sargasso Sea that not only synthesized carbohydrates but also vitamin D when exposed to sunlight (Holick, 1995). Approximately 400 million years ago, as vertebrates ventured from the ocean onto land, they were confronted with a significant crisis. Because they previously evolved in the calcium-rich ocean environment, they were able to utilize the abundant cations for signal transduction and a wide variety of cellular and metabolic processes. In addition, calcium became a major component of the skeleton of marine animals and provided the solid foundation for structural support.
However, the environment was deficient in calcium on land. When they lived in the ocean, early marine vertebrates could easily extract abundant amounts of cations from the ocean through specific calcium transport mechanisms in the gills or by simply absorbing it through their skin. As a result, the organisms that ventured onto land had to develop a new mechanism to utilize and process the scarce amounts of calcium in their environment in order to maintain their calcium-dependent cellular and metabolic activities and also satisfy the large requirement for calcium to mineralize their skeletons. The new strategy that developed resulted in the intestine evolving efficiently to absorb the calcium consumed in their diets. For reasons that remain unknown, an intimate relationship between sunlight and vitamin D evolved to play a critical role in regulating intestinal absorption of calcium from the diet to maintain a healthy mineralized skeleton and satisfy the body's requirement for this vital mineral (Holick, 2009).
In human evolutionary history, the ability to maintain vitamin D synthesis was closely associated with the evolution of skin pigmentation. The wide variation of human skin colors has long been of interest to the scientific community. Most theories claimed that melanin pigmentation was an adaptation to some attribute of the physical environment that varies primarily by latitude. Lighter pigments were necessary outside of the tropics in order to permit vitamin D synthesis in the skin due lower levels of ultraviolet (UV) radiation, whereas darkly pigmented skin provided protection against harmful levels of UV radiation in the equatorial regions (Jablonski, 2004). This background allows us to interpret vitamin D deficiency within the framework of Darwinian medicine as the result of an evolutionary mismatched or novel environment.
The ultimate explanation for why we are vulnerable to disease addresses the evolutionary basis of illness by examining evolved defenses, infections, novel environments, genes, and evolutionary legacies. An evolutionary explanation aims to show why humans in general are susceptible to some diseases and not to others. It seeks to answer "why?" questions about origins and functions by studying not only the evolution of a disease but the design characteristics that makes people vulnerable to that disease (Nesse and Williams, 6-7). Using this model, vitamin D deficiency can be seen as the consequence of people living in a novel environment compared to that of where their ancestors lived for tens of thousands of years. Rickets and a host of other health problems found in modern humans can be explained by vitamin D deficiency resulting from the environmental mismatch.
According Nesse and Williams, cold weather can be considered a novel environmental factor since Homo sapiens evolved and lived among the hot African savannahs for most its history. The spread of humans to other parts of the world with seasonally cold environments was facilitated by technological innovations such as fire and clothing which were achieved only a few tens of thousands of years ago. In cold environments, having the appropriate clothing and shelter brought its own health problems. Humans' natural synthesis of vitamin D is dependent on exposure of their skins to sunlight. However in a cold environment, being indoors for most of the day and covered by thick clothing when outside will greatly decrease the absorption of UV light and thus produce inadequate amounts of vitamin D (154-155).
As people began to migrating into city-centers in northern Europe during the Industrial Revolution, the growing pollution in the atmosphere in combination with the construction of multistoried structures in close proximity provided an environment for children that was devoid of direct exposure to sunlight. Doctors became aware of a bone-deforming disease in children that was endemic in Great Britain and northern Europe. The incidence of the disease commonly known as rickets or English disease continued to increase during this era. By the turn of the 20th century, this crippling bone disease was epidemic in industrialized cities of northern Europe and the northeastern United States (Holick, 2005). In United States, it was noticed that rickets struck black children at a higher rate than white children. From an biological standpoint, people who happen to have heavily pigmented skins would have admitted far less sunlight for vitamin D synthesis (Nesse and Williams, 155). Once foods were fortified with vitamin D and rickets appeared to have been conquered, many health care professionals thought the major health problems resulting from vitamin D deficiency had been resolved. However, the problem of vitamin D deficiency remains a major health issue today and this condition has been traced to susceptibility a wide variety of diseases.
It is now recognized and documented in this issue that vitamin D deficiency is one of the most common medical conditions in the world. It has been estimated that upwards of 30-50% of both children and adults in the United States, Canada, Mexico, Europe, Asia, New Zealand, and Australia are vitamin D deficient. The major reason for world-wide epidemic of vitamin D deficiency is the lack of appreciation that essentially none of our foods contains an adequate amount of vitamin D to satisfy the body's requirement which is now estimated to be 3,000-5,000 IU of vitamin D per day (Holick, 2009).
In recent years, scientists have begun seeing vitamin D as not a vitamin but as a hormone. Its metabolic product, calcitriol, is actually a secosteroid hormone that is the key that unlocks binding sites on the human genome. The human genome contains more than 2,700 binding sites for calcitriol. These binding sites are near genes involved in virtually every known major disease of humans (Norman, 2008). Vitamin D has received increased attention recently for its pleiotropic actions on many chronic diseases including cancer, cardiovascular disease, autoimmune disease, diabetes, and neurologic disease (Holick, 2005). It has been reported that vitamin D regulates over 900 genes. The importance of vitamin D on the regulation of cells of the immune system has gained increased appreciation over the past decade with the discovery of the vitamin D receptor (VDR) and key vitamin D metabolizing enzymes expressed by cells of the immune system. Animal studies, early epidemiologic and clinical studies have gathered much evidence of vitamin D's role in maintaining immune system balance.
One of the most exciting discoveries has shown that vitamin D creates cathelicidin, an antibiotic peptide produced by the immune system in response to pathogens (Kamen and Tangpricha 2010). In addition, research has shown that this ability has been preserved through approximately 60 million years of evolution and is shared only by primates, including humans - but no other known animal species. Scientists found the presence of a genetic element that is specific to primates and involved in the innate immune response. They found it not only in humans and their more recent primate ancestors, such as chimpanzees, but also in primates that split off on the evolutionary lineagae tens of millions of years ago, such as old world and new world primates. The genetic material, called an Alu element, is part of what used to be thought of as "junk DNA" and makes up more than 90 percent of the human genome. However, this genetic material is now understood to often play important roles in regulating and turning on the expression of other genes. The fact that this vitamin D mediated immune response has been retained through millions of years of evolutionary selection and is still found in species ranging from squirrel monkeys to baboons and humans, suggests that it must be critical to their survival (Gombart et al, 2009). The ramifications of these findings hold enormous potential in opening whole new era in the control and prevention of infectious disease, in particular influenza.
Lack of vitamin D synthesis has been theorized for high rates of influenza prevalence during winter. It is already know that UV radiation triggers vitamin D production in the skin and vitamin D deficiency is common in the winter. There is also historic evidence that influenza pandemics are associated with solar activity cycles. From this, it is hypothesized that influenza pandemics are associated with solar control of vitamin D levels in humans which waxes and wanes in concert with solar cycle dependent UV radiation (Hayes, 2010). About 2% of people have evidence of flu viruses in their systems during the summer, yet that seldom leads to outbreaks of the flu. It was also noted that the 1968 Hong Kong flu first showed up in Great Britain in August of that year, but the virus did not cause any significant summertime illness. But as the sun became progressively lower in the sky and the winter solstice arrived, the first community outbreaks occurred. As spring arrived, flu cases ebbed and virtually disappeared after the summer solstice, only to rise again in September 1969 and explode in the days before the winter solstice.
Activated vitamin D has been shown to act as an immune system modulator by preventing excessive expression of inflammatory cytokines and increasing the 'oxidative burst' potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection (Cannell et al, 2006). In one study, Japanese researchers reported that people taking vitamin D were three times less likely to report cold and flu symptoms. 354 children were given a daily dose of 1200 IUs of vitamin D over a period of three months. Vitamin D was found to protect against influenza A with the vitamin D group being 58 percent less likely to catch the disease. Vitamin D also appeared to suppress asthma attacks in children with a history of asthma (Urashima et al, 2010).
With last year's swine flu pandemic and likely possibility of future such outbreaks, if a source of resistance can be found in a single vitamin, the health and public policy ramifications would be tremendous. Current recommendations from the Institute of Medicine for adequate daily intake of vitamin D are 200 IU for children and adults up to 50 years of age, 400 IU for adults 51 to 70 years of age, and 600 IU for adults 71 years of age or older. However, most experts agree that without adequate sun exposure, children and adults require approximately 800 to1000 IU per day (Holick, 2007). There is a growing recognition that upper respiratory and middle ear infections in infants and young children emanates from a lack of vitamin D. Middle ear infections are very common in children, comprising a major reason for doctors' office visits, and low vitamin D levels have been linked with middle ear infections (Linday et al, 2008). Pediatricians now suggest vitamin D supplements for infants. National guidelines for vitamin D supplementation is almost certainly will have to be revised in light of these findings.
As many health problems linked to vitamin D has become known in recent years, the ultimate explanation for vitamin D deficiency helps explain why this happening. Because modern people live in novel environments than that of their ancestors and spend more time indoors, the opportunities to obtain the optimum amount of vitamin D production in the skin has greatly decreased to avoidance of the sun. As we learn more on how vitamin D maintains human health, scientists and physicians will learn how to better treat and prevent a host of modern diseases.
