Gene/Protein Disease Symptom Drug Enzyme Compound
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Vitamin D is very important for overall health and wellbeing. A major source of vitamin D comes from exposure to sunlight. Measurement of 25-hydroxyvitamin D in the blood and not 1,25-dihydroxyvitamin D is used to determine vitamin D status. A blood level of 25-hydroxyvitamin D of at least 20 ng/mL is considered to be vitamin D sufficient. Vitamin D deficiency increases the risk of many common cancers, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and type I diabetes.
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PMID:Vitamin D: important for prevention of osteoporosis, cardiovascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers. 1629 17

Evidence from animal models and prospective studies of RA, multiple sclerosis, and type-1 diabetes suggest an important role for vitamin D as a modifiable environmental factor in autoimmune disease. This role has not been well studied in human SLE. We compared serum 25-hydroxyvitamin D (25(OH)D) levels between recently diagnosed SLE cases and matched controls, and examined disease characteristics in relationship to 25(OH)D among cases. Data from a population-based cohort of 123 recently diagnosed SLE patients and 240 controls were used. We found a trend toward lower 25(OH)D levels in cases compared to controls, which was statistically significant in Caucasians (p=0.04), controlling for age, sex, season, and smoking. Overall, 67% of the subjects were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared to Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found in 22 of the SLE cases, with presence of renal disease being the strongest predictor (OR 13.3, p<0.01) followed by photosensitivity (OR 12.9, p<0.01). These results suggest vitamin D deficiency as a possible risk factor for SLE and provide guidance for future studies looking at a potential role of vitamin D in the prevention and/or treatment of SLE.
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PMID:Vitamin D deficiency in systemic lupus erythematosus. 1643 39

Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D-deficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer.
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PMID:Vitamin D physiology. 1656 71

Life expectancy for patients with Cystic Fibrosis (CF) has steadily improved during the last three decades, and death in childhood is now uncommon. Nutrition is a critical component of the management of CF, and nutritional status is directly associated with both pulmonary status and survival. Expert dietetic care is necessary, and attention must be given to ensuring an adequate energy intake in the face of demands which may be increased by inadequately controlled malabsorption, chronic broncho-pulmonary colonisation by bacteria and fungi, exacerbations of acute lung infection, impaired lung function, and the need for rehabilitation, repair and growth. Pancreatic enzyme replacement therapy (PERT) is needed by up to 90% of CF patients in Northern Europe, where the 'severe' mutation deltaF508 predominates, but a smaller proportion in Mediterranean countries and elsewhere, because pancreatic insufficiency is one of few features of CF which correlate with genotype. Complications of CF including liver disease and CF-related diabetes pose further challenges. In addition, deficiency of specific nutrients including fat soluble vitamins (particularly A, E and K) essential fatty acids and occasionally minerals occur for a variety of reasons. Osteopenia is common and poorly understood. Liver disease increases the likelihood of vitamin D deficiency. Glucose intolerance and diabetes affect at least 25% of CF adults, and the diabetes differs from both types 1 and 2 diabetes mellitus, but it inversely correlates with prognosis. Management consists of anticipating problems and addressing them vigorously as soon as they appear. Supplements of vitamins are routinely given. Energy supplements can be oral, enteral or, rarely, parenteral. All supplements, including PERT, are adjusted to individual needs.
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PMID:Cystic fibrosis: nutritional consequences and management. 1678 27

Vitamin D functions to regulate calcium homeostasis in intestine, kidney, and bone. Vitamin D deficiency during bone development causes rickets and in adults vitamin D deficiency, which has been shown to be common in the elderly population, can cause secondary hyperparathyroidism that can result in osteomalacia and increased risk of fracture. Recent evidence has suggested that vitamin D can have numerous other physiological functions including protection against certain autoimmune diseases, such as diabetes and multiple sclerosis and inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells. Exactly how vitamin D affects numerous different systems is a subject of continuing investigation. This article will review new developments related to the function and regulation of vitamin D target proteins in classic vitamin D target tissues that have provided novel insight into the mechanism of vitamin D action.
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PMID:New insights into the mechanisms involved in the pleiotropic actions of 1,25dihydroxyvitamin D3. 1683 19

This article provides practical advice about foods and dietary supplements that are beneficial for the health of older people. Overweight and obesity are among the most common nutrition-related disorders in older people. A plant-based diet is associated with reduced risk of chronic diseases such as obesity, cardiovascular disease, cancer, and diabetes. Vitamin B12 deficiency is prevalent in older adults, but there are misconceptions about the causes, consequences, and treatments. Diminished synthesis of vitamin D in the skin that occurs with aging and poor dietary intake contribute to the high prevalence of poor vitamin D status in older adults. Vitamin D deficiency is associated with chronic disorders beyond poor bone health. Supplements containing vitamin B12 and vitamin D will help older adults meet their needs for these key nutrients.
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PMID:Nutrition and aging--practical advice for healthy eating. 1684 55

Diabetes mellitus is associated with various organ dysfunctions through hyperglycemia, insulin deficiency, or advanced glycation end products, which can also cause impaired calcium homeostasis such as the reductions of parathyroid hormone secretion, vitamin D receptor (VDR) number, and 25- (OH) vitamin D-1 alpha-hydroxylase activity in the parathyroid gland, intestine, and kidney, respectively. On the contrary, abnormal calcium homeostasis such as vitamin D deficiency/insensitivity and hyperparathyroidism can cause glucose intolerance or diabetes. Vitamin D deficiency/insensitivity induces type 2 diabetes through impaired insulin secretion involving VDR on pancreatic beta cells, as well as type 1 diabetes through the reduction in immuno-modulatory action of 1,25 (OH)(2) vitamin D. Primary hyperparathyroidism induces glucose intolerance via insulin resistance due to elevated intracellular calcium in the targeted organ of insulin.
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PMID:[Calcium homeostasis and diabetes mellitus]. 1688 34

Frailty is a common condition in older people. It now can be objectively defined by the Fried criteria. When recognized, early intervention should begin with the institution of endurance, resistance, and balance exercises. In men with testosterone deficiency a trial of testosterone replacement should be considered. Vitamin D deficiency needs to be recognized and treated. Appropriate treatment of underlying diseases, such as anemia, diabetes mellitus, and congestive heart failure, are a key management principle. In people who have frailty aggressive health promotion and disease prevention techniques can lead to an inhibition of the downward spiral to disability.
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PMID:Frailty. 1696 45

The North American epidemic of overeating, combined with a sedentary lifestyle, has led to a growing prevalence of obesity, diabetes, and the "metabolic syndrome" in children. Excessive caloric intake does not imply adequate nutrition, and vitamin-deficiency syndromes still occur in some American children. Here we describe cases of scurvy and vitamin D deficiency in 2 children with cognitive disorders. Thorough dietary histories suggested the diagnosis in each patient and, had they been obtained at presentation, would likely have obviated invasive diagnostic workup, unnecessary stress to the patients and their families, and significant functional disability. Overnutrition and malnutrition may coexist, particularly among those with abnormal cognition or autistic spectrum disorders. Classic nutritional deficiencies must not be omitted from the differential diagnosis. A comprehensive dietary history and screening for vitamin deficiencies in at-risk children are important aspects of preventive health care and are essential for prompt diagnosis and treatment.
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PMID:Scurvy and rickets masked by chronic neurologic illness: revisiting "psychologic malnutrition". 1733 93

It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. More marginal vitamin D deficiency is likely to be a significant contributing factor to osteoporosis risk. However, recent emerging data from studies of adults suggest that low vitamin D status (serum 25-hydroxyvitamin D levels <50 nmol/l) may be contributing to the development of various chronic diseases, including cardiovascular disease, hypertension, diabetes mellitus, some inflammatory and autoimmune diseases, and certain cancers. Adequacy of vitamin D status in children and adolescents has been the focus of a number of recent investigations, and these studies have shown a high prevalence of low vitamin D status during the winter (especially in adolescents), with lower prevalence during the summer. Therefore, consideration of potential corrective strategies to allow children and adolescents to maintain adequate vitamin D status throughout the year, even in the absence of adequate summer sun exposure, is warranted.
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PMID:Vitamin D in childhood and adolescence. 1740 48


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