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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 vitamin D 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 compound that is present in very few foods from nature. Because of this, it is often added to products such as fortified milk and is available as a dietary supplement. The two major forms are vitamin D2, also known as ergocalciferol, and vitamin D3 or cholecalciferol (DeLuca, 2004). Vitamin D3 is also produced naturally in the human body when ultraviolet (UV) radiation from sunlight is absorbed through the skin (Holick, 2003). Vitamin D obtained either through consumption or sun exposure is initially biologically inert and must be converted in a two-step process to become activated. First, a hydroxylation reaction occurs in the liver that coverts vitamin D into 25-hydroxyvitamin D [25(OH)D], which is also known as calcidiol. In the next step, a second hydroxylation reaction is carried out in the kidneys that forms 1,25-dihydroxyvitamin D [1,25(OH)2D], which is also known as calcitriol (DeLuca, 2004; Holick, 2009).
In the human body, vitamin D aids in the absorption of calcium, which helps in the growth and development of bone. The mineralization of bone ensures normal blood levels of calcium and phosphorus. (DeLuca, 2008). Osteoblasts (cells that form bone) and osteoclasts (cells that absorb bone) also need vitamin D for bone growth and remodeling. Without sufficient vitamin D, bones weaken or deform. Vitamin D deficiency results in rickets in children and osteomalacia in adults. In conjunction with calcium, vitamin D also helps protect older adults from osteoporosis (Holick, 2004). 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).
It is known that the biosynthesis of vitamin D evolved over 750 million years ago though the full details on how this process initially occurred remains a mystery. It is believed that the phytoplankton Emeliani huxleii was among the first organisms 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 (Ca2+) for signal transduction and a wide variety of cellular and metabolic processes. In addition, calcium had become a major component of the skeleton of marine animals and provided the solid foundation for structural support (Holick, 2009).
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 obtain 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 calcium requirement 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 hypotheses claim that melanin pigmentation was an adaptation to some attribute of the physical environment that varies primarily by latitude (Jablonski, 2004). Modern humans first arose in sub-Saharan Africa approximately 100,000-150,000 years ago. Around 35,000-40,000 years ago, groups of them left the continent and moved northward, eventually settling in Europe. As these northbound migrants advanced to higher latitudes, they went through progressive depigmentation over time until they ultimately attained the light-colored appearance of that of contemporary northern Europeans. This pigmentary transformation occurred as a result of a physiological adaptation to the less intense UV radiation at those higher latitudes. Melanin is known have properties as a natural sunscreen and the melanin of dark-skinned individuals would have hindered the absorption of UV radiation and inhibited the vitamin D synthesis (Jablonksi and Chaplin, 2000).
Natural selection would have favored genes for lighter skin at northern latitudes. Dark-skinned individuals would have been at greater risk of vitamin D deficiency, thus more susceptible to developing rickets. Rickets would have seriously handicapped mobility and the ability to forage for food and avoid predators. In other words, because rickets imperiled survival and reproductive fitness, it acted as selective pressure for lighter skin. Lighter pigments were necessary outside of the tropics in order to permit vitamin D synthesis in the skin due lower levels of ultraviolet radiation, whereas darkly pigmented skin provided protection against harmful levels of UV radiation in the equatorial regions (Jablonksi and Chaplin, 2000; 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 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 became known as rickets or English disease and 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 African-American children at a higher rate than Caucasian 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 not as 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 recently received increased attention 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 unique ability has been preserved through approximately 60 million years of evolution within the primate lineage but in no other known animal species. Scientists discovered the presence of a genetic element involved in the internal immune response that was found only in primates including humans. This genetic material is called an Alu element and is part of what used to be considered "junk DNA". However, this genetic material is now understood to have an important role in the regulation and expression of other genes. Because this vitamin D-initiated immune feature has been preserved through natural selection for tens of millions of years and is still found in a wide range of primates today, it is strongly implied that this ability was essential for their survival (Gombart et al, 2009). The ramifications of these findings hold enormous potential in changing the ways in how health practitioners control and prevent infectious disease such as 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 but that rarely leads to a flu outbreak. 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. However by the time the winter solstice arrived and the sun's rays have weakened, the first community outbreaks occurred. When spring arrived, flu cases waned and virtually disappeared after the summer solstice, only to rise again in September 1969 and dramatically spike in the days before the winter solstice (Cannell et al, 2006).
Activated vitamin D has been shown to act as an immune system modulator by preventing excessive expression of inflammatory cytokines. 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). It has been increasingly recognized that lack of vitamin D has been responsible for upper respiratory and middle ear infections in infants and young children. 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). Because of these findings, pediatricians now recommend infants to be given vitamin D supplements.
As many health problems linked to vitamin D have 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 due avoidance of the sun. In many ways, contemporary culture promotes the message that the sun is something to be avoided. As vitamin D deficiency has been documented to be more prevalent than previously thought, the many problems associated with it are being noticed by the medical and scientific communities (Holick, 2007). As we learn more on how vitamin D maintains human health, scientists and physicians will be given a new tool to better treat and prevent a host of modern diseases.