Concept Of Vitamin Research Articles

AB005. Vitamin D in children—role beyond bones

: Vitamin D is a fat-soluble steroid hormone that contributes to the maintenance of normal calcium homeostasis and skeletal mineralization. The prevalence of subclinical vitamin D deficiency is not only restricted to rural population, but it is highly prevalent across the whole globe. It affects the individuals irrespective of their gender, race and geography. It’s deficiency is common in all age groups including the neonates. Although, it is commonly known as vitamin, but is actually not an essential dietary vitamin in the strict sense, as it can be easily synthesized by all mammals from sunlight in adequate amount. Vitamin D not only plays an essential role in calcium homeostasis and bone mineral metabolism, but it also helps in performing a wide range of fundamental biological functions such as cell differentiation, inhibition of cell growth and immunomodulation. By inhibiting uncontrolled proliferation and stimulation of cell differentiation, Vitamin D helps to prevent development of autoimmune disorders and even common cancers. Prolonged usage of certain drugs (Glucocorticoids, cytochrome P450 enzyme inducers, anticonvulsants, antiretro viral agents etc.) and other health problems including chronic kidney disease, asthma, pneumonia, coeliac disease, liver disease, tuberculosis, cancers (prostate, breast and colon), diabetes etc. are associated with Vitamin D deficiency. The concept of vitamin D possessing important pleiotropic actions and owing to its multiple implications on health, the epidemic of vitamin D deficiency significantly contributes to the burden on the healthcare system and society. Thus, it is desirable to update our knowledge about current research related to role of vitamin D beyond bone metabolism.

Understanding fibrosis in eosinophilic esophagitis: Are we there yet?

Eosinophilic esophagitis (EoE) is an immune/antigen-mediated, progressive fibrostenotic disease characterized by symptoms of esophageal dysfunction and abnormal eosinophilic infiltration in the esophagus. Despite current treatment modalities of dietary antigen elimination or topical corticosteroids, a subset of patients do not have clinical or histologic response. Even with resolution of superficial epithelial eosinophilia, patients may still have progressive subepithelial fibrosis, which may lead to esophageal strictures over time. Histologic identification of subepithelial fibrosis requires deep esophageal biopsies, which are not routinely obtained. Herein, we review the challenges in diagnosing and treating fibrosis in EoE. We propose the novel concept of vitamin D supplementation to treat fibrosis in EoE through downregulation of profibrotic mediator, transforming growth factor-beta.

The Concept of Vitamin D Sufficiency and Insufficiency in Graves’ Disease

Graves’ disease (GD) is an autoimmune disorder of the thyroid gland resulting from dysregulation of the immune system against this important endocrine gland. The disease is characterized by hyperthyroidism and presence of circulation auto antibody which stimulates the Thyroid Hormone Receptor(TSHR). The auto antibody is also responsible for goiter and other extra-thyroidal manifestation like ophthalmic, dermatological and others. Vitamin D (Vit.-D) deficiency is reported to link with variety of autoimmune diseases. However the relation between thyroid autoimmunity of Graves’ disease and Vitamin D deficiency is still not very clear. But in some studies10-12, it was found that there is strong correlation between thyroid autoimmunity and vitamin D – 1,25-(OH) deficiency in newly diagnosed GD. It was found < 15 pmol/L. In one study it was found <12.5pmol/ L. According to definition of insufficiency or deficiency most of the Author agreed to describe insufficiency when Vit D level is less than 30pmol/L and deficient when less than 20 pmol/L. Vitamin D Receptor gene polymorphism is also associated with increased risk of Graves’ (4D) disease and higher volume of goiter. In other studies it was found that, the increased thyroid antibody titer was associated with Vitamin D deficiency. Some other studies showed that, treatment with Vitamin D in GD there is significant early improvement of the diseases. Meta-analysis showed low Vitamin D was also associated with higher risk of development of GD. Moreover, hyperthyroidism leading to osteoporosis in GD is also associated with low Vitamin D level and improves by treatment with Vitamin D. However, whether Vitamin D deficiency or insufficiency favor’s the onset of GD or supplementation of Vitamin D has any beneficial effect, needs further research.Birdem Med J 2017; 7(2): 160-163

Vitamin D and diabetes mellitus: an update 2013.

Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

Safety Issues of Vitamin D Supplementation

Vitamin D deficiency is a re-emerging global health problem, which is primarily due to inadequate vitamin D synthesis in the skin. Supplement use is an effective measure to improve vitamin D status. However, some safety issues have to be considered, which are highlighted in this review article: The concept of vitamin D safety consists of two models, the safe tolerable upper intake level (UL) method, and the idea of adequate circulating 25-hydroxyvitamin D (25[OH]D) levels. Oral vitamin D intakes up to 250 μg/d have not been associated with harm. Hypercalcemia, the hallmark of vitamin D intoxication, may only occur if circulating 25(OH)D levels are consistently above 375-500 nmol/l. However, some observational studies indicate that already circulating 25(OH)D levels > 125 nmol/l are related to an increased morbidity and mortality risk. Therefore, the Institute of Medicine has set the UL for adults at 100 μg/d, and the adequate circulating 25(OH)D level at 50 to 125 nmol/l. In clinical practice, oral vitamin D dosing has to consider that the increment in circulating 25(OH)D depends on baseline 25(OH)D levels and the person's body weight. It is reasonable to assess 25(OH)D before and 3-6 months after initiation of oral vitamin D administration and to adjust the dose, if necessary. In future, two issues have to be clarified: First, would it be more appropriate to define instead of a fixed UL a variable UL, based on the individual's body weight? Second, what are the underlying mechanisms, if any, for potentially harmful vitamin D effects at circulating 25(OH)D levels between 125 and 375 nmol/l.

The ‘Cocaine Blues' and Other Problems in Epidemiologic Studies of Vitamin D and Cancer

Compelling evidence from epidemiologic and laboratory studies and from clinical trials indicates that vitamin D metabolites decrease the risk of several common cancers. To set the stage for future progress in the area of vitamin D and cancer risk, it is imperative to clear the stage of encumbrances that have retarded progress. This introduction highlights six key areas that have been sources of confusion: 1) the difference between vitamins and hormones, 2) the meaning of the term vitamin “deficiency”, 3) the need for an explicit understanding of which form of vitamin D pertains to what hypothesis, 4) the timing of vitamin D exposure with respect to cancer risk, 5) the mechanism(s) of action of vitamin D metabolites, and 6) the difference between disease prevention and therapy with vitamin D metabolites. Many of these topics have been the subjects of recent reviews. Vitamins are essential substances required for normal functioning that the body cannot manufacture and therefore must consume; an example is vitamin C, a deficiency of which causes the disease scurvy. Conversely, hormones are essential substances that are synthesized in one part of the body, transferred via the blood, and exert effects at distant sites. 1,25(OH)2D is the result of synthesis in the skin that begins when ultraviolet radiation converts 7-dehydrocholesterol to vitamin D3 (cholecalciferol). Vitamin D3 subsequently undergoes two hydroxylations, the first in the liver, forming 25-(OH)vitamin D, which has little biologic activity, and the second in the kidney and in extra-renal sites, forming 1,25(OH)2D, the active vitamin D metabolite. 1,25(OH)2D exerts numerous effects in the body, classically on bone and mineral homeostasis, and therefore it is a hormone. Conversely, because cholecalciferol is synthesized in the skin following ultraviolet radiation, it is not a vitamin. Arguably, “vitamin D” could be considered a vitamin among African Americans. This is because persons with darkly pigmented skin make much less vitamin D from the same amount of solar exposure as persons with lightly pigmented skin since melanin, the major pigment in human skin, absorbs ultraviolet light and inhibits vitamin D synthesis. Consequently, the prevalence of hypovitaminosis D in the United States is much higher among African Americans than among Caucasian Americans. Profound vitamin D deficiency during childhood causes the bone-deforming disease rickets. Consequently, vitamin D deficiency historically was defined in terms of bone; the absence of rickets in childhood or the absence of osteomalacia in adulthood was considered to represent vitamin D sufficiency. However, the recognition that many “non-classical” organs, such as the prostate gland, respond to and even synthesize the vitamin D hormone, mandates that the concept of vitamin D deficiency be revised. In short, vitamin D “deficiency” is most meaningful with respect to a specific end point: the amount of vitamin D sufficient to maintain a normal skeleton is likely insufficient to maintain the differentiated phenotype of prostate and other cells. Scientific acceptance of the hypothesis that vitamin D metabolites inhibit the development of cancer faced several obstacles. Chief among these was the difficulty in understanding how differences in serum levels of vitamin D metabolites could influence the behavior of “nonclassical” cells, even though such cells possessed receptors for 1,25(OH)2D (vitamin D receptors, or VDR). This is because, unlike serum levels of 25(OH)D, which are known to decrease with distance from the equator and are lower among persons with dark pigmentation, serum levels of 1,25(OH)2D are tightly regulated and do not vary with geographic latitude or race. This difficulty was effectively removed by the demonstration that normal prostate cells (and, by inference, other “non-classical” cells) possess the enzyme 25-(OH)vitamin D-1hydroxylase and, like the kidney, synthesize 1,25(OH)2D from circulating levels of 25(OH)D. The autocrine synthesis of 1,25(OH)2D was subsequently shown for many other organs, such as the colon, breast, and pancreas, and is Dr. Schwartz is with the Departments of Cancer Biology and Epidemiology and Prevention, Wake Forest University, Winston-Salem, North Carolina, USA. Please address all correspondence to: Dr. Gary Schwartz, Departments of Cancer Biology and Epidemiology and Prevention, Wake Forest University, Medical Center Blvd., Winston-Salem, NC 27157, USA; Phone: 336-716-7446; Fax: 336-716-5687; E-mail: gschwart@wfubmc.edu. doi: 10.1301/nr.2007.aug.S75–S76

The Role of Vitamin D in the Prevention and Treatment of Osteoporosis

Vitamin D is essential for preventing and treating osteoporosis. Vitamin D enhances intestinal calcium absorption to help maintain blood calcium concentrations, necessary for bone mineralization and for muscle and nerve function. Vitamin D is metabolized to 25-hydroxyvitamin D (25OHD) in the liver and to the active form, 1,25-dihydroxyvitamin D [1,25(OH)2D] in the kidney. Inadequate vitamin D status contributes to increased bone turnover, secondary hyperparathyroidism, bone loss, fractures, muscle weakness, osteomalacia, and rickets in children. Vitamin D is synthesized in the skin upon exposure to sunlight. It is also found naturally in some foods and is present in fortified foods, in nonprescription supplements containing other vitamins or calcium, and as pure vitamin D in prescription and nonprescription forms. The concept of vitamin D adequacy has evolved well beyond the need for vitamin D for preventing rickets. Recommendations for vitamin D intake were increased in 1997 but continue to be debated. The best measure of vitamin D status is serum 25OHD, and recent studies suggest this should be at least 32 ng/mL. Many people fall short of this. Risks for poor vitamin D status include advanced age, minimal sun exposure, mal-absorption, and darkly pigmented skin. However, recent work suggests that many otherwise healthy individuals are inadequate in vitamin D. Although best known for its role in skeletal health, other roles for vitamin D in cancer, immunologic disease, and other aspects of health are being explored. Greater understanding of its role in skeletal health and overall well-being, and better avenues for assuring vitamin D adequacy for all people, are needed.

Vitamin D regulation of the renin-angiotensin system.

The renin-angiotensin system (RAS) plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis. Epidemiological and clinical studies have long suggested an association of inadequate sunlight exposure or low serum 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels with high blood pressure and/or high plasma renin activity, but the mechanism is not understood. Our recent discovery that 1,25(OH)(2)D(3) functions as a potent negative endocrine regulator of renin gene expression provides some insights into the mechanism. The concept of vitamin D regulation of blood pressure through the RAS opens a new avenue to our understanding of the physiological functions of the vitamin D endocrine system, and provides a basis for exploring the potential use of vitamin D analogues in prevention and treatment of hypertension.

Vitamin D nutrition and bone disease in adults.

The consequences of vitamin D deficiency upon the skeleton are well known and management in the absence of renal failure is relatively straightforward. Vitamin D, either by mouth or parenterally will correct the deficiency and heal the osteomalacia. The mechanisms underlying the causation of vitamin D deficiency are now better understood and indicate the importance of underlying calcium malabsorption and secondary hyperparathyroidism leading to 1,25(OH)2D-induced catabolism of 25(OH)D and possibly also of vitamin D itself. In such situations, e.g., gastrointestinal and pancreaticobiliary disease, calcium supplementation in addition to vitamin D is indicated. The reasons behind nutritional vitamin D deficiency and the possible role of meat in protecting from osteomalacia await further elucidation, but from epidemiological studies, calcium deficiency, per se, is not implicated in the etiopathogenesis. The concept of vitamin D insufficiency is poorly understood, and difficult to define since a single value or close range of serum 25(OH)D values is unlikely to predict the needs of all subjects. Oral calcium intake and renal function are also likely to be relevant to the level of 25(OH)D which is found to be sufficient or insufficient for any given individual to maintain a normal serum calcium level without secondary hyperparathyroidism. There is increasing evidence that vitamin D insufficiency, by leading to sustained hyperparathyroidism, is prejudicial to the skeleton, particularly cortical bone. Since it is without symptoms until fractures occur, it should be actively sought in those clinical situations now recognized as contributing to risk. It can only be identified by the periodic measurement of serum 25(OH)D and the calcitropic hormones PTH and 1,25(OH)2D. In addition, BMD should be measured in a predominantly cortical site such as the proximal forearm, as well as the more conventional sites of spine and hip. The implications of these recommendations are an increase in the use of assays for PTH and vitamin D metabolites in the groups of subjects discussed in this review. Patients with chronic malabsorption states might reasonably be expected to have measurements performed twice-yearly. When vitamin D insufficiency is found, treatment with either vitamin D, calcium or both will be necessary, depending on the etiology of the insufficiency state in the inividual. In some malabsorptive states, calcium malabsorption is the cause of hyperparathyroidism and oral calcium alone can be used to reverse excess PTH activity in those with an adequate state of vitamin D nutrition. However, even in those vitamin D replete individuals, vitamin D catabolism will be enhanced and a small additional oral dose of vitamin D can do no harm. Regular monitoring of PTH and vitamin D metabolites will remain a necessity to ensure continued efficacy of treatment. Current recommendations for dietary supplements of vitamin D are clearly inadequate [61]. There is compelling evidence for supplements of 800 IU per day in the elderly and other high risk populations. Such a dose is safe and without side effects. The available evidence suggests that this should be combined with calcium supplements of 1200 mg/day [19] and that the current UK recommendations for a daily calcium intake of 700 mg contrast with those from the USA at 1,200 mg for people over 50 years old. Physicians need to be aware of both the small but important problem of vitamin D depletion and osteomalacia with its sometimes ambiguous presentation, and the more common but covert vitamin D (and calcium) insufficiency with its widespread and varied clinical associations.

Michalos' Comments on Meeting Needs Disposed of

Can x need y without our being in a position to conceptualize y? Nothing, given ten seconds thought, is easier to show. Every man, woman, and child from the beginning of the human race needed Vitamin C as one ingredient in the minimum provisions for their food. It was only in this century, however, that people arrived at the concept of Vitamin C and became able to assert the need for it. On the record, we may expect more such discoveries.

Gedanken über einige Vitamine und eine zeitgemäße Vitaminkunde

Certain aspects of the present state of vitamin research are treated with special regard to a modern interpretation of the concept of vitamin and to questions concerning the utilization of recent findings by the food industry and other sciences. A classification of vitamins according to their solubility and functional properties is discussed. Recent findings on the relationships between tocopherols and tocotrienols and on bioquinones are dealt with. Furthermore, the significance of some vitamin-like substances (such as choline, S-methylmethionine and pangamic acid) and their biochemical importance for the animal and the human organism are considered.