Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population.
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Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. As the number of people with VDD continues to increase, the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research. VDD is very common in all age groups. As few foods contain vitamin D, guidelines recommended supplementation at suggested daily intake and tolerable upper limit levels. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency.
Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. In this review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and understand its biology and clinical implications. INTRODUCTION Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD).– This pandemic of hypovitaminosis D can mainly be attributed to lifestyle and environmental factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. Black people absorb more UVB in the melanin of their skin than do white people and, therefore, require more sun exposure to produce the same amount of vitamin D.
The high prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. Emerging research supports the possible role of vitamin D against cancer, heart disease, fractures and falls, autoimmune diseases, influenza, type-2 diabetes, and depression. Many health care providers have increased their recommendations for vitamin D supplementation to at least 1000 IU.
A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. In this review, we will focus on the biology of vitamin D and summarize the mechanisms that are presumed to underlie the relationship between vitamin D and its clinical implications.
Biology of the sunshine vitamin Vitamin D is unique because it can be made in the skin from exposure to sunlight.,– Vitamin D exists in two forms. Vitamin D 2 is obtained from the UV irradiation of the yeast sterol ergosterol and is found naturally in sun-exposed mushrooms. UVB light from the sun strikes the skin, and humans synthesize vitamin D 3, so it is the most “natural” form. Human beings do not make vitamin D 2, and most oil-rich fish such as salmon, mackerel, and herring contain vitamin D 3. Vitamin D (D represents D 2, or D 3, or both) that is ingested is incorporated into chylomicrons, which are absorbed into the lymphatic system and enter the venous blood. Vitamin D that comes from the skin or diet is biologically inert and requires its first hydroxylation in the liver by the vitamin D-25-hydroxylase (25-OHase) to 25(OH)D., However, 25(OH)D requires a further hydroxylation in the kidneys by the 25(OH)D-1-OHase (CYP27B1) to form the biologically active form of vitamin D 1,25(OH)2D., 1,25(OH)2D stimulates intestinal calcium absorption.
Without vitamin D, only 10–15% of dietary calcium and about 60% of phosphorus are absorbed. Vitamin D deficiency: Prevalence VDD has been historically defined and recently recommended by the Institute of Medicine (IOM) as a 25(OH)D of less than 0.8 IU. Vitamin D insufficiency has been defined as a 25(OH)D of 21–29 ng/mL.,– Children and young- and middle-aged adults are at equally high risk for VDD and insufficiency worldwide. VDD is common in Australia, the Middle East, India, Africa, and South America., Pregnant and lactating women who take a prenatal vitamin and a calcium supplement with vitamin D remain at high risk for VDD.–. Vitamin D deficiency, why it happens? Vitamin D deficiency: Consequences VDD results in abnormalities in calcium, phosphorus, and bone metabolism. VDD causes a decrease in the absorption of dietary calcium and phosphorus, resulting in an increase in PTH levels., The PTH-mediated increase in osteoclastic activity creates local foci of bone weakness and causes a generalized decrease in bone mineral density (BMD), resulting in osteopenia and osteoporosis.
An inadequate calcium–phosphorus product causes a mineralization defect in the skeleton., In young children who have little mineral in their skeleton, this defect results in a variety of skeletal deformities classically known as rickets., VDD also causes muscle weakness; affected children have difficulty in standing and walking, whereas the elderly have increasing sway and more frequent falls, thereby increasing their risk of fracture. Breastfed infants Vitamin D requirements cannot ordinarily be met by human milk alone, which provides. People who are obese or who have undergone gastric bypass surgery A BMI value of ≥30 is associated with lower serum 25(OH)D levels compared with nonobese individuals. Obese people may need larger than usual intakes of vitamin D to achieve 25(OH)D levels comparable to those of normal weight. Greater amounts of subcutaneous fat sequester (captivate) more of the vitamin and alter its release into the circulation.
Individuals who have undergone gastric bypass surgery may become vitamin D deficient over time without a sufficient intake of vitamin D from food or supplements; moreover part of the upper small intestine where vitamin D is absorbed is bypassed.,. Vitamin D synthesis Vitamin D undergoes two hydroxylations in the body for activation. Calcitriol (1,25-dihydroxyvitamin D 3), the active form of vitamin D, has a half-life of about 15 h, while calcidiol (25-hydroxyvitamin D 3) has a half-life of about 15 days. Vitamin D binds to receptors located throughout the body. Cancer Vitamin D decreases cell proliferation and increases cell differentiation, stops the growth of new blood vessels, and has significant anti-inflammatory effects., Many studies have suggested a link between low vitamin D levels and an increased risk of cancer, with the strongest evidence for colorectal cancer. In the Health Professionals Follow-up Study (HPFS), subjects with high vitamin D concentrations were half as likely to be diagnosed with colon cancer as those with low concentrations.
A definitive conclusion cannot yet be made about the association between vitamin D concentration and cancer risk, but results from many studies are promising. There is some evidence linking higher vitamin D intake to a lower risk for breast cancer. The effect of menopausal status on this association is still unclear. Heart disease Several studies are providing evidence that the protective effect of vitamin D on the heart could be via the renin–angiotensin hormone system, through the suppression of inflammation, or directly on the cells of the heart and blood-vessel walls. In the Framingham Heart Study, patients with low vitamin D concentrations (30 ng/mL). Hypertension The third National Health and Nutrition Examination Survey (NHANES-III), which is representative of the noninstitutionalized US civilian population, showed that systolic blood pressure and pulse pressure were inversely and significantly correlated with 25(OH)D levels among 12,644 participants.
Obesity Low concentrations of circulating vitamin D are common with obesity and may represent a potential mechanism explaining the elevated risk of certain cancers and cardiovascular outcomes. Levels of 25(OH)D are inversely associated with BMI, waist circumference, and body fat but are positively associated with age, lean body mass, and vitamin D intake. The prevalence of VDD is higher in black versus white children regardless of season predictors of VDD in children include black race, female sex, pre-pubertal status, and winter/spring season. Weight loss is associated with an increase in 25(OH)D levels among postmenopausal overweight or obese women. Fractures and falls Vitamin D is known to help the body absorb calcium, and it plays a role in bone health. In addition, VDRs are located on the fast-twitch muscle fibers, which are the first to respond in a fall.
It is theorized that vitamin D may increase muscle strength, thereby preventing falls. Many studies have shown an association between low vitamin D concentrations and an increased risk of fractures and falls in older adults. A combined analysis of 12 fracture-prevention trials found that supplementation with about 800 IU of vitamin D per day reduced hip and nonspinal fractures by about 20%, and that supplementation with about 400 IU per day showed no benefit.
Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University have examined the best trials of vitamin D versus placebo for falls. Their conclusion is that “fall risk reduction begins at 700 IU and increases progressively with higher doses.”. Autoimmune diseases VDD can contribute to autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, rheumatoid arthritis, and autoimmune thyroid disease. A prospective study of white subjects found that those with the highest vitamin D concentrations had a 62% lower risk of developing MS versus those with the lowest concentrations.
A Finnish study that followed children from birth noted that those given vitamin D supplements during infancy had a nearly 90% lower risk of developing type 1 diabetes compared with children who did not receive supplements. Pelvic floor disorders The frequency of Pelvic floor disorders, including urinary and fecal incontinence, is increasing with age. Pelvic floor disorders have been linked to osteoporosis and low BMD and remain one of the most common reasons for gynaecologic surgery, with a failure rate of 30%. Subnormal levels of 25(OH)D are common among women, and lower levels are associated with a higher likelihood of pelvic floor disorders. Results from the National Health and Nutrition Examination Survey confirmed that lower 25(OH) D levels are associated with a greater risk for urinary incontinence in women older than 50 years.
ESCP suggests that the maintenance tolerable upper limits (UL) of vitamin D, which is not to be exceeded without medical supervision, should be 1000 IU/d for infants up to 6 months, 1500 IU/d for infants from 6 months to 1 year, at least 2500 IU/d for children aged 1–3 years, 3000 IU/d for children aged 4–8 years, and 4000 IU/d for everyone over 8 years. Higher levels of 2000 IU/d for children 0–1 year, 4000 IU/d for children 1–18 years, and 10000 IU/d for children and adults 19 years and older may be needed to correct VDD. CONCLUSION Numbers of people with VDD are continuously increasing; the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research.
VDD is very common in all age groups. Very few foods contain vitamin D therefore guidelines recommended supplementation of vitamin D at tolerable UL levels. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D 2 or vitamin D 3 is recommended for the deficient patients.
More research is required to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
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