I'd definition, contraction of I would or I had. Dec 30, 2013 The Dragonlance Campaign Setting is a 3.5 sourcebook, published by Wizards of the Coast in 2003. Technically a 1st-party book, it received no further official support, with the production of future sourcebooks delegated to Margaret Weis in charge of Sovereign Press.
(D 3) Class identifiers Use, Clinical data External links Vitamin D is a group of fat-soluble responsible for increasing intestinal absorption of, and, and multiple other biological effects. In humans, the most important compounds in this group are vitamin D 3 (also known as ) and vitamin D 2. Cholecalciferol and ergocalciferol can be ingested from the diet and from supplements. Only a few foods contain vitamin D. The major natural source of the vitamin is synthesis of cholecalciferol in the skin from through a chemical reaction that is dependent on (specifically ). Dietary recommendations typically assume that all of a person's vitamin D is taken by mouth, as sun exposure in the population is variable and recommendations about the amount of sun exposure that is safe are uncertain in view of the risk. Vitamin D from the diet or skin synthesis is biologically inactive; enzymatic conversion in the liver and kidney is required for activation.
As vitamin D can be synthesized in adequate amounts by most mammals exposed to sufficient sunlight, it is not an essential dietary factor, and so not technically a. Instead it could be considered a, with activation of the vitamin D pro-hormone resulting in the active form, which then produces effects via a in multiple locations. Cholecalciferol is converted in the liver to (25-hydroxycholecalciferol); is converted to 25-hydroxyergocalciferol. These two vitamin D metabolites (called 25-hydroxyvitamin D or 25(OH)D) are measured in serum to determine a person's vitamin D status. Calcifediol is further hydroxylated by the kidneys to form (also known as 1,25-dihydroxycholecalciferol), the biologically active form of vitamin D. Calcitriol circulates as a hormone in the blood, having a major role regulating the concentration of and, and promoting the healthy growth and remodeling of bone.
Calcitriol also has other effects, including some on cell growth, neuromuscular and immune functions, and reduction of inflammation. Vitamin D has a significant role in and metabolism. Its discovery was due to effort to find the dietary substance lacking in children with (the childhood form of ). Vitamin D supplements are given to treat or to prevent osteomalacia and rickets, but the evidence for other health effects of vitamin D supplementation in the general population is inconsistent. The effect of vitamin D supplementation on mortality is not clear, with one meta-analysis finding a small decrease in mortality in elderly people, and another concluding no clear justification exists for recommending supplementation for preventing many diseases, and that further research of similar design is unneeded in these areas. Contents.
Types Name Chemical composition Structure Vitamin D 1 Mixture of molecular compounds of with, 1:1 Vitamin D 2 (made from ) Vitamin D 3 (made from in the skin). Vitamin D 4 Vitamin D 5 (made from ) Several forms of vitamin D exist. The two major forms are vitamin D 2 or ergocalciferol, and vitamin D 3 or cholecalciferol; vitamin D without a subscript refers to either D 2 or D 3 or both. These are known collectively as calciferol. Vitamin D 2 was chemically characterized in 1931. In 1935, the of vitamin D 3 was established and proven to result from the of 7-dehydrocholesterol.
Chemically, the various forms of vitamin D are, i.e., in which one of the bonds in the steroid rings is broken. The structural difference between vitamin D 2 and vitamin D 3 is the side chain of D 2 contains a between carbons 22 and 23, and a on carbon 24.
In the human body. The role of active vitamin D (1,25-dihydroxyvitamin D, calcitriol) is shown in orange. The active vitamin D metabolite calcitriol mediates its biological effects by binding to the (VDR), which is principally located in the of target cells. The binding of calcitriol to the VDR allows the VDR to act as a that modulates the of transport proteins (such as and ), which are involved in calcium absorption in the intestine. The vitamin D receptor belongs to the superfamily of, and VDRs are expressed by cells in most, including the, skin,. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and ) and to the maintenance of bone content. One of the most important roles of vitamin D is to maintain skeletal calcium balance by promoting in the intestines, promoting by increasing number, maintaining calcium and phosphate levels for, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels.
Can result in lower and an increased risk of reduced bone density or because a lack of vitamin D alters mineral metabolism in the body. Thus, vitamin D is also critical for through its role as a potent stimulator of. The VDR regulates. Vitamin D also affects the immune system, and VDRs are expressed in several, including and activated. In vitro, vitamin D increases expression of the gene in cells, and affects the synthesis of,.
Deficiency. Main article: A diet deficient in vitamin D in conjunction with inadequate sun exposure causes osteomalacia (or rickets when it occurs in children), which is a softening of the bones. In the developed world, this is a rare disease. However, has become a worldwide problem in the elderly and remains common in children and adults. Low blood calcifediol (25-hydroxy-vitamin D) can result from avoiding the sun. Deficiency results in impaired bone mineralization and bone damage which leads to bone-softening diseases, including. Being deficient in vitamin D can cause intestinal absorption of dietary calcium to fall to 15%.
When not deficient, an individual usually absorbs between 60-80%. Bone health Rickets. Main article:, a childhood disease, is characterized by impeded growth and soft, weak, deformed that bend and bow under their weight as children start to walk. This condition is characterized by bow legs, which can be caused by calcium or phosphorus deficiency, as well as a lack of vitamin D; today, it is largely found in low-income countries in Africa, Asia, or the Middle East and in those with genetic disorders such as pseudovitamin D deficiency rickets.
Maternal may cause overt bone disease from before birth and impairment of bone quality after birth. Nutritional rickets exists in countries with intense year-round sunlight such as Nigeria and can occur without vitamin D deficiency. Although rickets and osteomalacia are now rare in Britain, outbreaks have happened in some immigrant communities in which osteomalacia sufferers included women with seemingly adequate daylight outdoor exposure wearing Western clothing. Having darker skin and reduced exposure to sunshine did not produce rickets unless the diet deviated from a Western omnivore pattern characterized by high intakes of meat, fish, and eggs, and low intakes of high-extraction. The dietary risk factors for rickets include abstaining from animal foods.
Vitamin D deficiency remains the main cause of rickets among young infants in most countries, because breast milk is low in vitamin D and social customs and climatic conditions can prevent adequate sun exposure. In sunny countries such as Nigeria, South Africa, and Bangladesh, where rickets occurs among older toddlers and children, it has been attributed to low dietary calcium intakes, which are characteristic of cereal-based diets with limited access to dairy products. Rickets was formerly a major public health problem among the US population; in, where ultraviolet rays are about 20% stronger than at sea level on the same latitude, almost two-thirds of 500 children had mild rickets in the late 1920s. An increase in the proportion of animal protein in the 20th century American diet coupled with increased consumption of milk fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases. Also, in the United States and Canada, vitamin D-fortified milk, infant vitamin supplements, and vitamin supplements have helped to eradicate the majority of cases of rickets for children with fat malabsorption conditions.
Osteoporosis and osteomalacia. Main article: is a disease in adults that results from vitamin D deficiency. Characteristics of this disease are softening of the bones, leading to bending of the spine, bowing of the legs, muscle weakness, bone fragility, and increased risk for fractures. Osteomalacia reduces calcium absorption and increases calcium loss from bone, which increases the risk for bone fractures.
Osteomalacia is usually present when 25-hydroxyvitamin D levels are less than about 10 ng/mL. Although the effects of osteomalacia are thought to contribute to chronic, there is no persuasive evidence of lower vitamin D levels in chronic pain sufferers or that supplementation alleviates chronic nonspecific musculoskeletal pain. Skin pigmentation Dark-skinned people living in temperate climates have been shown to have low vitamin D levels but the significance of this is not certain. Dark-skinned people may be less efficient at making vitamin D because melanin in the skin hinders vitamin D synthesis. Non-bone diseases Mortality, all cause Use of supplements The effects of vitamin D supplementation on health are uncertain.
A 2013 review did not find any effect from supplementation on the rates of disease, other than a tentative decrease in mortality in the elderly. Vitamin D supplements do not alter the outcomes for, or, cancer, or knee. Low vitamin D levels may result from disease rather than cause disease. A United States report states: 'Outcomes related to, and, and and metabolic syndrome, falls and physical performance, immune functioning and, infections, neuropsychological functioning, and could not be linked reliably with calcium or vitamin D intake and were often conflicting.' : 5 Some researchers claim the IOM was too definitive in its recommendations and made a mathematical mistake when calculating the blood level of vitamin D associated with bone health. Members of the IOM panel maintain that they used a 'standard procedure for dietary recommendations' and that the report is solidly based on the data.
Research on vitamin D supplements, including large-scale clinical trials, is continuing. Mortality, all-cause Vitamin D 3 supplementation has been tentatively found to lead to a reduced risk of death in the elderly, but the effect has not been deemed pronounced or certain enough to make taking supplements recommendable.
Other forms (vitamin D 2, alfacalcidol, and calcitriol) do not appear to have any beneficial effects with regard to the risk of death. High blood levels appear to be associated with a lower risk of death, but it is unclear if supplementation can result in this benefit. Both an excess and a deficiency in vitamin D appear to cause abnormal functioning and premature aging. The relationship between serum calcifediol level and all-cause mortality is parabolic. Harm from vitamin D appears to occur at a lower vitamin D level in the black population than in the white population.: 435 Bone health In general, no good evidence supports the commonly held belief that vitamin D supplements can help prevent. Its general use for prevention of this disease in those without vitamin D deficiency is thus likely not needed.
For older people with osteoporosis, taking vitamin D with calcium may help prevent hip fractures, but it also slightly increases the risk of stomach and kidney problems. Supplementation with higher doses of vitamin D, in those older than 65 years, may decrease fracture risk. The effect is small or none for people living independently. Low serum vitamin D levels have been associated with, and low. Taking extra vitamin D, however, does not appear to change the risk.
Athletes who are vitamin D deficient are at an increased risk of and/or major breaks, particularly those engaging in contact sports. Main article: In general, vitamin D 2 is found in and vitamin D 3 is found in animals. Vitamin D 2 is produced by ultraviolet irradiation of found in many fungi. The vitamin D 2 content in mushrooms and, a lichen, increase with exposure to ultraviolet light. This process is emulated by industrial ultraviolet lamps, concentrating vitamin D 2 levels to higher levels. The reports D 2 and D 3 content combined in one value.
Fungal sources. C. Arbuscula , dry: vitamin D 3 0.67 to 2.04 μg/g (27 to 82 IU/g); vitamin D 2 0.22-0.55 μg/g (8.8 to 22 IU/g). 25-49 Recommendations on recommended 25(OH)D serum levels vary across authorities, and vary based on factors like age. US labs generally report 25(OH)D levels in ng/mL.
Other countries often use nmol/L. One ng/mL is approximately equal to 2.5 nmol/L. A 2014 review concluded that the most advantageous serum levels for 25(OH)D for all outcomes appeared to be close to 30 ng/mL (75 nmol/L). The optimal vitamin D levels are still controversial and another review concluded that ranges from 30 to 40 ng/mL (75 to 100 nmol/L) were to be recommended for athletes. Part of the controversy is because numerous studies have found differences in serum levels of 25(OH)D between ethnic groups; studies point to genetic as well as environmental reasons behind these variations. Supplementation to achieve these standard levels could cause harmful vascular.
A 2012 showed that the risk of increases when blood levels of vitamin D are lowest in a range of 8 to 24 ng/mL (20 to 60 nmol/L), although results among the studies analyzed were inconsistent. In 2011 an committee concluded a serum 25(OH)D level of 20 ng/mL (50 nmol/L) is needed for bone and overall health. The dietary reference intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure the specified levels of intake achieve the desired serum 25(OH)D levels in almost all persons. No contributions to serum 25(OH)D level are assumed from sun exposure and the recommendations are fully applicable to people with or negligible exposure to sunlight. The Institute found serum 25(OH)D concentrations above 30 ng/mL (75 nmol/L) are 'not consistently associated with increased benefit'. Serum 25(OH)D levels above 50 ng/mL (125 nmol/L) may be cause for concern. However, some people with serum 25(OH)D between 30 and 50 ng/mL (75 nmol/L-125 nmol/L) will also have inadequate vitamin D.
Further information: Vitamin D toxicity is rare. It is caused by supplementing with high doses of vitamin D rather than sunlight. The threshold for vitamin D toxicity has not been established; however, according to some research, the tolerable upper intake level (UL) is 4,000 /day for ages 9–71 (100 µg/day), while other research concludes that, in healthy adults, sustained intake of more than 1250 μg/day (50,000 IU) can produce overt after several months and can increase serum 25-hydroxyvitamin D levels to 150 ng/mL and greater.
Those with certain medical conditions, such as primary, are far more sensitive to vitamin D and develop in response to any increase in vitamin D nutrition, while maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of mental retardation and facial deformities. A review published in 2015 noted that adverse effects have been reported only at 25(OH)D serum concentrations above 200 nmol/L. Published cases of toxicity involving hypercalcemia in which the vitamin D dose and the 25-hydroxy-vitamin D levels are known all involve an intake of ≥40,000 IU (1,000 μg) per day. Pregnant or breastfeeding women should consult a doctor before taking a vitamin D supplement.
The FDA advised manufacturers of liquid vitamin D supplements that droppers accompanying these products should be clearly and accurately marked for 400 (1 IU is the biological equivalent of 25 ng cholecalciferol/ergocalciferol). In addition, for products intended for infants, the FDA recommends the dropper hold no more than 400 IU. For infants (birth to 12 months), the tolerable upper limit (maximum amount that can be tolerated without harm) is set at 25 μg/day (1,000 IU). One thousand micrograms per day in infants has produced toxicity within one month.
After being commissioned by the Canadian and American governments, the (IOM) as of 30 November 2010, has increased the tolerable upper limit (UL) to 2,500 IU per day for ages 1–3 years, 3,000 IU per day for ages 4–8 years and 4,000 IU per day for ages 9–71+ years (including pregnant or lactating women). Calcitriol itself is auto-regulated in a cycle, and is also affected by, calcium, and phosphate. Effect of excess Vitamin D overdose causes hypercalcemia, which is a strong indication of vitamin D toxicity – this can be noted with an increase in urination and thirst.
If hypercalcemia is not treated, it results in excess deposits of calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain and organ damage. The main symptoms of vitamin D overdose which are those of hypercalcemia including, nausea, and vomiting. These may be followed by, weakness, insomnia, nervousness, and ultimately. Furthermore, and (especially in the kidneys) may develop. Other symptoms of vitamin D toxicity include mental retardation in young children, abnormal bone growth and formation, diarrhea, irritability, weight loss, and severe depression. Vitamin D toxicity is treated by discontinuing vitamin D supplementation and restricting calcium intake.
Kidney damage may be irreversible. Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.
The concentrations of vitamin D precursors produced in the skin reach an, and any further vitamin D produced is degraded. Biosynthesis Synthesis of vitamin D in nature is dependent on the presence of UV radiation and subsequent activation in liver and in kidney.
Many animals synthesize vitamin D 3 from, and many fungi synthesize vitamin D 2 from. Interactive pathway Click on icon in lower right corner to open. Click on genes, proteins and metabolites below to link to respective articles.
Thermal isomerization of to vitamin D 3 The transformation that converts 7-dehydrocholesterol to vitamin D 3 occurs in two steps. First, 7-dehydrocholesterol is by ultraviolet light in a 6-electron ring-opening; the product is. Second, previtamin D 3 spontaneously to vitamin D 3 in an. At room temperature, the transformation of previtamin D 3 to vitamin D 3 in an organic solvent takes about 12 days to complete.
The conversion of previtamin D 3 to vitamin D 3 in the skin is about 10 times faster than in an organic solvent. The conversion from ergosterol to vitamin D 2 follows a similar procedure, forming previtamin D 2 by photolysis, which isomerizes to vitamin D 2. The transformation of previtamin D 2 to vitamin D 2 in methanol has a rate comparable to that of previtamin D 3. The process is faster in white button mushrooms. 3) Synthesis in the skin. In the epidermal strata of the skin, vitamin D production is greatest in the stratum basale (colored red in the illustration) and stratum spinosum (colored light brown). Vitamin D 3 is produced photochemically from 7-dehydrocholesterol in the skin of most vertebrate animals, including humans.
The precursor of vitamin D 3, 7-dehydrocholesterol is produced in relatively large quantities. 7-Dehydrocholesterol reacts with at between 270 and 300 nm, with peak synthesis occurring between 295 and 297 nm. These wavelengths are present in sunlight, as well as in the light emitted by the UV lamps in (which produce ultraviolet primarily in the spectrum, but typically produce 4% to 10% of the total UV emissions as UVB). Exposure to light through windows is insufficient because glass almost completely blocks UVB light. Adequate amounts of vitamin D can be produced with moderate sun exposure to the face, arms and legs, averaging 5–30 minutes twice per week, or approximately 25% of the time for minimal sunburn. The darker the skin, and the weaker the sunlight, the more minutes of exposure are needed.
Vitamin D overdose is impossible from UV exposure; the skin reaches an equilibrium where the vitamin degrades as fast as it is created. Absorbs or reflects ultraviolet light and prevents much of it from reaching the skin. Sunscreen with a sun protection factor (SPF) of 8 based on the UVB spectrum decreases vitamin D synthetic capacity by 95%, and SPF 15 decreases it by 98%. The skin consists of two primary layers: the inner layer called the, composed largely of, and the outer, thinner.
Thick epidermis in the soles and palms consists of five strata; from outer to inner, they are: the,. Vitamin D is produced in the of two innermost strata, the stratum basale and stratum spinosum. Evolution Vitamin D can be synthesized only by a photochemical process. Phytoplankton in the ocean (such as and ) have been photosynthesizing vitamin D for more than 500 million years. Primitive vertebrates in the ocean could absorb calcium from the ocean into their skeletons and eat plankton rich in vitamin D.
Land vertebrates required another source of vitamin D other than plants for their calcified skeletons. They had to either ingest it or be exposed to sunlight to photosynthesize it in their skin. Land vertebrates have been photosynthesizing vitamin D for more than 350 million years. In birds and fur-bearing mammals, fur or feathers block UV rays from reaching the skin. Instead, vitamin D is created from oily secretions of the skin deposited onto the feathers or fur, and is obtained orally during grooming.
However, some animals, such as the, are naturally cholecalciferol-deficient, as serum 25-OH vitamin D levels are undetectable. Industrial synthesis Vitamin D 3 (cholecalciferol) is produced industrially by exposing to UVB light, followed by purification.
The 7-dehydrocholesterol is a natural substance in fish organs, especially the liver, or in wool grease from sheep. Vitamin D 2 (ergocalciferol) is produced in a similar way using ergosterol from yeast or mushrooms as a starting material. Mechanism of action Metabolic activation. Kidney hydroxylation of calcifediol to Vitamin D is carried in the bloodstream to the liver, where it is converted into the. Circulating calcifediol may then be converted into, the biologically active form of vitamin D, in the kidneys. Whether it is made in the skin or ingested, Vitamin D is in the at position 25 (upper right of the molecule) to form 25-hydroxycholecalciferol (calcifediol or 25(OH)D). This reaction is catalyzed by the enzyme, the product of the CYP2R1 human gene, and expressed.
Once made, the product is released into the, where it is bound to an α-globulin carrier protein named the. Calcifediol is transported to the proximal tubules of the kidneys, where it is hydroxylated at the 1-α position (lower right of the molecule) to form calcitriol (1,25-dihydroxycholecalciferol, 1,25(OH) 2D). The conversion of calcifediol to calcitriol is catalyzed by the enzyme, which is the product of the CYP27B1 human gene. The activity of CYP27B1 is increased by, and also by low calcium or phosphate. Following the final converting step in the kidney, calcitriol is released into the circulation.
By binding to vitamin D-binding protein, calcitriol is transported throughout the body, including to the classical target organs of intestine, kidney and bone. Calcitriol is the most potent natural of the, which mediates most of the physiological actions of vitamin D. In addition to the kidneys, calcitriol is also synthesized by certain other cells including - in the. When synthesized by monocyte-macrophages, calcitriol acts locally as a, modulating body defenses against microbial invaders by stimulating the. Inactivation The activity of calcifediol and calcitriol can be reduced by hydroxylation at position 24 by, forming secalciferol and calcitetrol respecively. Difference between substrates Vitamin D 2 (ergocalciferol) and Vitamin D 3 (cholecaliferol) share a similar mechanism of action as outlined above.
Metabolites produced by vitamin D 2 is sometimes named with a er- or ergo prefix to differentiate them from the D 3-based counterparts. Nevertheless, these differences are present in the metabolism of Vitamin D 2 and Vitamin D 3:. Metabolites produced from Vitamin D 2 tend to bind less well to the vitamin D-binding protein. Vitamin D 3 can alternatively be hydroxylated to calcifediol by (CYP27A1), but Vitamin D 2 can not. Ergocalciferol can be directly hydroxylated at position 24.
The inactivation also tends to have a more profound effect: while calcitriol's activity decreases to 60% of original after 24-hydroxylation, ercalcitriol suffers a 10-fold decrease in activity on conversion to ercalcitetrol. History American researchers and in 1914 discovered a substance in which later was called 'vitamin A'.
British doctor noticed dogs that were fed cod liver oil did not develop rickets and concluded vitamin A, or a closely associated factor, could prevent the disease. In 1922, Elmer McCollum tested modified cod liver oil in which the vitamin A had been destroyed. The modified oil cured the sick dogs, so McCollum concluded the factor in cod liver oil which cured rickets was distinct from vitamin A. He called it vitamin D because it was the fourth vitamin to be named. It was not initially realized that, unlike other vitamins, vitamin D can be synthesised by humans through exposure to UV light.
In 1925, it was established that when 7-dehydrocholesterol is irradiated with light, a form of a vitamin is produced (now known as D 3). Stated: 'Light equals vitamin D.'
, at the in Germany, received the in 1928 for his work on the constitution of sterols and their connection with vitamins. In 1929, a group at in Hampstead, London, were working on the structure of vitamin D, which was still unknown, as well as the structure of steroids. A meeting took place with, and to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated the sterol molecules were flat, not as proposed by the German team led by Windaus.
In 1932, Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. The informal academic collaboration between the team members, Otto Rosenheim, Harold King, and was very productive and led to the isolation and characterization of vitamin D. At this time, the policy of the was not to patent discoveries, believing the results of medical research should be open to everybody.
In the 1930s, Windaus clarified further the chemical structure of vitamin D. In 1923, American biochemist at the demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials. After irradiating rodent food, Steenbock discovered the rodents were cured of rickets. A vitamin D deficiency is a known cause of rickets. Using $300 of his own money, Steenbock patented his invention. His irradiation technique was used for foodstuffs, most memorably for milk. By the expiration of his patent in 1945, rickets had been all but eliminated in the US.
In 1969, after studying nuclear fragments of intestinal cells, a specific binding protein for Vitamin D called the was identified by Mark Haussler. In 1971–72, the further metabolism of vitamin D to active forms was discovered.
In the liver, vitamin D was found to be converted to calcifediol. Calcifediol is then converted by the kidneys to calcitriol, the biologically active form of vitamin D. Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. The vitamin D metabolites, calcifediol and calcitriol, were identified by competing teams led by in the laboratory of and by Tony Norman and colleagues.
Research There is considerable research activity looking at effects of vitamin D and its metabolites in animal models, cell systems, gene expression studies, epidemiology and clinical therapeutics. These different types of studies can produce conflicting evidence as to the benefits of interventions with vitamin D. One school of thought contends the human physiology is fine-tuned to an intake of 4,000–12,000 IU/day from sun exposure with concomitant serum 25-hydroxyvitamin D levels of 40 to 80 ng/mL and this is required for optimal health. Proponents of this view, who include some members of the panel that drafted a now-superseded 1997 report on vitamin D from the IOM, contend the IOM's warning about serum concentrations above 50 ng/mL lacks biological plausibility. They suggest, for some people, reducing the risk of preventable disease requires a higher level of vitamin D than that recommended by the IOM.
The United States Office of Dietary Supplements established a Vitamin D Initiative in 2014 to track current research and provide education to consumers. In their 2016 review, they recognise that a growing body of research suggests that vitamin D might play some role in the prevention and treatment of types 1 and 2 diabetes, glucose intolerance, hypertension, multiple sclerosis, and other medical conditions. They state further: 'however, most evidence for these roles comes from in vitro, animal, and epidemiological studies, not the randomized clinical trials considered to be more definitive. Until such trials are conducted, the implications of the available evidence for public health and patient care will be debated'.
Some preliminary studies link low vitamin D levels with disease later in life. Evidence as of 2013 is insufficient to determine whether vitamin D affects the risk of cancer. One meta-analysis found a decrease in mortality in elderly people.
Another meta-analysis covering over 350,000 people concluded that vitamin D supplementation in unselected community-dwelling individuals does not reduce skeletal (total fracture) or non-skeletal outcomes (myocardial infarction, ischaemic heart disease, stroke, cerebrovascular disease, cancer) by more than 15%, and that further research trials with similar design are unlikely to change these conclusions. Vitamin D deficiency is widespread in the European population. European research is assessing vitamin D intake levels in association with disease rates and policies of dietary recommendations, food fortification, vitamin D supplementation, and small amounts of sun exposure. Apart from VDR activation, various alternative mechanisms of action are under study, such as inhibition of by, a hormone involved in. References.
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Any similarity to actual people, organizations, places, or events is purely coincidental. ©2000 Wizards of the Coast, Inc. Made in the U.S.A. Game is a game about hero es. Th rough imagination, storytelling and fellowship, you can explore what it means to be a hero. One of the most exciting and rewarding parts of the game is listening to the quiet voice of your inner hero, allowing some part of your own special potential to rise to the sur- face and reveal itself.
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In short, you’ll develop everything that happened to your character before his or her first adventure. You’ll have a better handle on how you view the world— and what the world thinks of you. And you’ll know what goals you’re working toward. We’ll start where all D&D characters traditionally start: with six numbers between 3 and 18 written on scratch paper. The Rolling Your Ability Scores chapter helps you make those difficult choices.
You’ll learn just what the od ds are on roll ing that 18, what to d o if you get unusually low scores, and suggestions on how to roleplay a character whose abilities are much dif- ferent than your own. At the heart of the character generation process is the Choosing Your Race and Class chapter. After all, when most people are asked what kind of D&D char- acter they have, they reply “I’m an elven thief” or “I’m a human barbarian.” This chapter discusses each of the race/class combinations available to 1st-level characters, providing tips for maximizing your char- acter’s potential, tips for roleplaying them, and some unusual variants for each race and class.
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