Progress In Vitamin Research Articles

Vitamin D: Controversy Cancer and Beyond

Vitamins are an essential part to wellbeing. This was not something always known however, as the Germ theory was the accepted thesis of the 18th century. It was found that certain accessory factors helped mitigate and even cure these diseases such as beriberi, scurvy, and rickets. Accessory factors, later coined vitamins by Casimir Funk, are an essential constituent of the human diet. Vitamin D is technically not a vitamin but functions as a steroid hormone whose most well-known purpose is calcification of the human skeleton. This helps prevent osteomalacia in adults and rickets, a serious problem in children due to their developmental stages. But besides its well-known role, vitamin D also has other important non-calcification purposes, including being a possible anticancer agent. Calcitriol (1,25 dihydroxycholecalciferol, vitamin D3) has found to treat certain cancers in various ways: from the VDR-RXR complex to analogs being able to decrease tumor growth, lowering expression of stem cell marker genes, and inhibition of the Wnt pathway. Although there is promise in its effectiveness based on studies of squamous cell carcinoma, prostate, breast, colon, and ovarian cancer; hypercalcemia, lack of consistent data, and insufficient clinical trials are serious issues that constantly get in the way of progression of vitamin D’s legitimacy as a solution.

Recent progress of vitamin C in management of sepsis

Sepsis is frequently associated with multi-system organ dysfunction and refractory hypotension, leading to a high mortality and poor prognosis. As an antioxidant, ascorbic acid (vitamin C) is an important auxiliary factor for many enzymes in the organism. Numerous studies have revealed that vitamin C can attenuate the inflammatory response, improve microcirculatory and hypotension in sepsis, and also can enhance the role of catecholamine in central nervous system, to prevent sepsis-induced organ failure and improve prognosis of patients. Key words: Sepsis; Ascorbic acid; Antioxidants

Update on recent progress in vitamin D research. Development of novel Vitamin D Derivatives.

Vitamin D3 plays important roles in many physiological processes, including calcium and phosphate homeostasis, bone metabolism, and immune regulation. An active form of vitamin D3, 1α,25(OH)2D3, binds to vitamin D nuclear receptor(VDR, vitamin D receptor), and regulates expression of specific target genes. Thousands of vitamin D3 analogs have been synthesized, and the structure-activity relationships of secosteroidal compounds have been examined in detail. On the other hand, development of non-secosteroidal VDR ligands remains limited, and only a few non-secosteroidal VDR ligands with potent activity have been reported so far. Development of novel structures with unique biological profiles would enable the new clinical application of vitamin D function.

Update on recent progress in vitamin D research. Vitamin D and bone, mineral metabolism.

Vitamin D endocrine system is required for bone and mineral homeostasis through the active form of vitamin D[1α,25(OH)2D3]transported to the target organs, where the vitamin D receptor(VDR)is present. The biological significance of 1α,25(OH)2D3-VDR signalling is regarded not only in classical target of vitamin D involved in calcium and phosphate homeostasis, such as intestine, bone, kidney and parathyroid glands, but also in many other non-classical target cells of vitamin D including skin keratinocytes, pancreatic β cells, cardiomyocytes, T-lymphocytes, bone marrow macrophages, among others. Although 1α,25(OH)2D3-VDR signalling in classical target organs of vitamin D has been extensively studied, its precise function in these target organs still needs further investigation.

Update on recent progress in vitamin D research. Eldecalcitol and intestinal calcium absorption.

Though various physiological actions have been attributed to vitamin D, its most important function is to promote absorption of calcium from the intestinal tract. While the absorption rate of calcium is generally low, it tends to decline further with age. In addition, calcium intake is decreasing in recent years in Japan. Therefore, it is important to increase the intestinal calcium absorption rate. Eldecalcitol has been shown to increase calcium absorption from the intestinal tract, suppress bone resorption, increase bone mineral density, and prevent fractures. Elocalcitol use leads to a lower systemic active vitamin D[1α,25(OH)2D]concentration, compared to that with alfacalcidol use. This is because eldecalcitol inhibits vitamin D activation in the kidney. Therefore, it is presumed that the calcium absorption-boosting effect of eldecalcitol is not due to the action of 1α, 25(OH)2D, but due to eldecalcitol itself.

Update on recent progress in vitamin D research. The effects of vitamin D in autoinflammatory diseases.

Various kinds of immune cells -including dendritic cells, macrophages, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase(CYP27B1). In vitro studies have shown the anti-inflammatory effect of 1,25-dihydroxyvitamin D:the active form of vitamin D. As vitamin D deficiency spread in our society, epidemiological studies have established the association between vitamin D deficiency and incidence or progression of several inflammatory diseases, including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and multiple sclerosis(MS). In addition, recently the property of vitamin D for treatment or prevention is debated. Here, we review the recent epidemiological evidence associated with vitamin D and inflammatory diseases, and describe the immunomodulatory effect of vitamin D underlying it.

Update on recent progress in vitamin D research. Vitamin D Metabolism and Its Regulation.

Vitamin D is taken up from food as D2 and D3. Vitamin D3 is also synthesized from 7-dehydrocholesterol in the skin by the exposure of ultraviolet B. The D2 and D3, which are called native vitamin D, are hydroxylated at C25 in the liver by CYP2R1 and then at C1 in the kidney by CYP27B1, to be converted to an active vitamin D metabolite, 1,25-dihydroxyvitamin D[1,25(OH)2D]. CYP24A1 converts 25-hydroxyvitamin D(25OHD)and 1,25(OH)2D to 24,25-dihydroxyvitamin D[24,25(OH)2D]and 1,24,25-trihydroxyvitamin D[1,24,25(OH)3D], respectively, to decrease the level of 1,25(OH)2D. CYP27B1 and CYP24A1 are mainly expressed in the kidney but also detected in other tissues, and it is suggested that 1,25(OH)2D produced in the extra-renal tissues may exert its effects locally.

Update on recent progress in vitamin D research. Vitamin D and metabolic disease.

Numerous epidemiological studies and meta-analyses have indicated that there is a link between Vitamin D insufficiency/deficiency and metabolic disorders such as type 1 and type 2 diabetes mellitus as well as metabolic syndrome. However, vitamin D supplementation has not demonstrated improvement effects in obesity, disorders of glucose and lipid metabolism in any of these illnesses;therefore, the details of the causal relationship remain unclear. Improvement in glucose metabolism was observed in a study in which only vitamin D deficient patients with 25-hydroxyvitamin D[25(OH)D]levels of less than 20 ng/mL were given native vitamin D supplementation. Further studies are needed to determine the 25(OH)D level at which intervention is needed along with the required amount and duration of such supplementation.

Update on recent progress in vitamin D research. Treatment of metabolic bone disorders by vitamin D.

Vitamin D is indispensable for bone health and calcium metabolism, and decreased action of vitamin D causes various abnormalities in bone metabolism. Severe vitamin D deficiency causes osteomalacia/rickets. Even milder vitamin D insufficiency could still be harmful for bone health via secondary hyperparathyroidism and bone loss, and could also lead to increased risk of falling. Osteomalacia/rickets associated with impaired vitamin D action should be treated by either native or active vitamin D3, depending on its etiology. As for osteoporosis, vitamin D repletion is important to adequate therapeutic effects of anti-resorptives. As a monotherapy, eldecalcitol, active vitamin D3 analogue, has been shown to increase bone mineral density and to decrease the incidence of vertebral fractures with significantly greater efficacy compared to active vitamin D3.

Update on recent progress in vitamin D research. Vitamin D treatment for hypoparathyroidism.

The patients with hypoparathyroidism have been treated with active vitamin D(ie, alfacalcidol and calcitriol). Parathyroid hormone(PTH)increases extracellular calcium concentration partly through the activation of vitamin D, and active vitamin D corrects hypocalcemia mainly by increasing intestinal calcium abosorption. PTH coordinately increases blood calcium level with vitamin D in bone and kidney, however, renal tubular reabsorption of calcium is regulated by PTH-dependent mechanism. Hypercalciuria is an complication of long-term vitamin D treatment for PTH-deficient hypoparathyroidism.

Update on recent progress in vitamin D research. EldecalcitolR and Fall Prevention.

In the elderly, vitamin D deficiency results not only in impaired bone mineralization, but also myopathy. Low vitamin D has also been shown to be associated with decline of muscle strength, sarcopenia, functional limitation, and disability. Several recent studies have shown that low serum vitamin D concentration is associated with lower physical function and falls in older adults. In this article, the author reviews a relationship between falls and serum vitamin D concentration of the elderly living in the community, and also introduces the major results from a recent randomized controlled trial on prevention of decline of fall-related balance performance by the treatment with newly developed active vitamin D(EldecalcitolR )among the women with age 65 years old and over and diagnosed as osteoporosis.

Update on recent progress in vitamin D research. Vitamin D insufficiency/deficiency.

Serum 25(OH)D level reflects bodily vitamin D store. Recently published "Assessment criteria for vitamin D deficiency/insufficiency in Japan" defines vitamin D sufficiency as 25(OH)D level of 30 ng/mL or more, vitamin D insufficiency as that of 20 to 30 ng/mL, vitamin D deficiency as that of less than 20 ng/mL. The lower the serum 25(OH)D level is, the higher the risks are, of secondary hyperparathyroidism, low bone mineral density, fall, fracture, rickets/osteomalacia, and hypocalcemia, as well as lower response to anti-osteoporosis medications. Beyond musculoskeletal disorders, vitamin D insufficiency/deficiency has been shown to be associated with various immunological, metabolic, and malignant disorders mainly by basic and epidemiological studies.

Prowess in vitamin A deficiency

Vitamin A deficiency is one of the world's three major micronutrient deficiency diseases,and xerophthalmia, night blindness are the only awareness of it in many clinicians'views.However,the advancements of the current study of its effect are far more than the traditional epithelial and ophthalmic parts.In fact,the progress in vitamin A closely associated to the clinic,especially the diarrhea,recurrent respiratory tract infections,anemia etc is more outstanding.Because there are many different factors in suffering from diverse diseases among people all over the world,it needs to consider more considerately and roundly when prevent,diagnose and treat those diseases correlated to vitamin A.Now the progress of this part is reviewed. Key words: Vitamin A deficiency; Vitamin A supplementation; Diarrhea; Recurrent respiratory tract infections; Anemia

Progress of vitamin E metabolic engineering in plants

Vitamin E is important for human and animal health. Many human diseases, such as certain cancers and neurodegenerative and cardiovascular disease, are associated with the insufficient intake of vitamin E. The daily requirements for vitamin E in men and women have been increased to 15-30 mg. Because the primary source of dietary vitamin E comes from plants, there is a need to increase vitamin E production through plant engineering in order to meet the demand in human consumption. Numerous studies have been carried out in this field, leading to many successful examples. In this review, we summarized the recent progress in vitamin E metabolic engineering in plants aimed at improving the vitamin E content and regulating composition of vitamin E.

Reduced mannose incorporation into GDP-mannose and dolichol-linked intermediates of N-glycosylation in hamster liver during vitamin A deficiency

The molecular mechanism of reduced incorporation of radioactively labeled mannose into hamster liver glycoconjugates during the progression of vitamin A deficiency was investigated. In particular the in vivo incorporation of [2-3H]mannose into GDP-mannose, dolichyl phosphate mannose (Dol-P-Man), lipid-linked oligosaccharides, and glycopeptides of hamster liver was examined. Hamsters maintained on a vitamin A-free diet showed a reduction in the incorporation of mannose into GDP-mannose about 10 days before clinical signs of vitamin A deficiency could be observed. The decrease in [2-3H]mannose incorporated into GDP-mannose was accompanied by a reduction in label incorporated into Dol-P-Man, lipid linked oligosaccharides and glycopeptides, which became more severe with the progression of vitamin A deficiency. By the time they reached a plateau stage of growth, hamsters fed the vitamin A-free diet showed a 50% reduction in the amount of [2-3H]mannose converted to GDP-mannose, and the radioactivity associated with Dol-P-Man and glycopeptides was reduced by approximately 60% as compared to retinoic acid-supplemented controls. These results strongly indicate that the reduced incorporation of mannose into lipidic intermediates and glycoproteins observed during vitamin A deficiency is due to impaired GDP-mannose synthesis.

Adipose Tissues and Vitamin E

1. Vitamin E content in the adipose tissue was examined in rats with and without vitamin E deficiency. With the progression of vitamin E depletion, the more rapid decrease in tocopherol concentration was observed in brown adipose tissue (BAT) than in white adipose tissue (WAT), and the rate of decrease of tocopherol was approximately three times faster in BAT than in WAT. After the intramuscular administration of 10 mg/kg of all-rac-tocopheryl acetate twice a week for two weeks to vitamin E-deficient rats, a similar pattern of increase was observed in the tocopherol concentrations of BAT and WAT, although the rate of increase was slower in WAT than in BAT. 2. Changes of tocopherol concentration in BAT and WAT were investigated in normo-nourished rats with hyperlipemia produced by the intramuscular injection of Triton WR-1339 for 7 days. A marked increase in tocopherol concentration was observed in both BAT and WAT in the late period of hyperlipemia, with the increase being greater in WAT. 3. The fatty acid composition of adipose tissue was compared between rats with and without vitamin E deficiency. No significant differences were observed in BAT and WAT between the two groups. 4. The glucose uptake of WAT was not altered in vitamin E-deficient rats when compared with control rats.

Liver and Plasma Levels of Descarboxyprothrombin (PIVKA II) in Vitamin K Deficiency in Rats

Descarboxyprothrombin (PIVKA II) is a precursor of prothrombin without biological activity, and it increases with vitamin K deficiency. We studied the time course changes in liver and plasma levels of PIVKA II during the progress of vitamin K deficiency in rats. Good correlation was observed between liver PIVKA II and plasma PIVKA II and between liver or plasma PIVKA II and plasma prothrombin in experiments In which rats were fed a vitamin K-deficlent diet. Feeding of a vitamin K-deficient diet or fasting caused marked Increases in liver and plasma PIVKA II In male rats and a weaker response in female rats. Warfarin, a vitamin K antagonist, caused an abrupt increase in liver PIVKA II, but the Increase In plasma PIVKA II was delayed about 3 hr. Plasma prothrombin decreased from about 30 min later. Factor VII decreased similarly to prothrombin, and changes in the prothrombin time and activated partial thromboplastin time were slower than the changes in these substances. Sex differences were not seen in these warfarin actions. These observations indicate that liver and plasma PIVKA II are sensitive markers of vitamin K deficiency in rats, and assay of PIVKA II can be useful for analyzing the action mechanism of drugs which Influence blood coagulation.

The role of vitamin D in the medullary bone formation in egg-laying Japanese quail and in immature male chicks treated with sex hormones.

The effect of vitamin D3 on medullary bone formation was investigated in egg-laying Japanese quail and in immature male chicks treated with sex hormones. When laying quail were fed a vitamin D-deficient diet for 16 days, their eggshell weights and egg production rate were markedly reduced in a time-dependent manner with a significant decrease in plasma calcium and 25-hydroxyvitamin D3 levels. The calcium content of the medullary bone of femurs decreased markedly with the progress of vitamin D deficiency, whereas that of the cortical bone remained unchanged. Quantitative histological examination also showed that the area of the mineralized portion of medullary bone in quail that were fed the vitamin D-deficient diet markedly decreased compared with that in the control laying quail, whereas the total area of the mineralized and unmineralized portions of medullary bone in the bone marrow cavity increased moderately. Daily administration of vitamin D3 (0.75 microgram/day) to the vitamin D-deficient quail increased the mineralization of medullary bone as early as day 4. Daily administration of both estradiol (0.3 mg/day) and testosterone (0.9 mg/day) for 3 weeks to immature male chicks induced an apparent hypercalcemia and matrix formation of medullary bone, regardless of the vitamin D status of the chicks. Mineralization of medullary bone was observed only when vitamin D3 was administered together with the sex hormones. These results suggest that vitamin D3 is directly involved in the mineralization of medullary bone in birds.