The role of vitamin D in selected autoimmune diseases.

The authors of recently published scientific papers are focusing increasingly often on the effect of vitamin D on immune processes. In the case of deficiencies of this vitamin, an imbalance in the immune system is observed, which is associated with the intensification of the inflammatory reaction in the body and the increased possibility of an autoimmune reaction. Therefore, due to the growing interest of scientists in the relationship between the effects of vitamin D and the development of autoimmune diseases, this paper considers the use of Vitamin D in autoimmune therapies. However, the mechanism of vitamin D on individual autoimmune diseases has not been elucidated so far, therefore there is a need for further research. The importance of maintaining normal plasma vitamin D levels to reduce the risk of developing autoimmune diseases has been demonstrated by the authors of other studies. They showed that vitamin D levels influenced the course, severity of symptoms and frequency of relapses of autoimmune thyroid disease, inflammatory bowel disease, and rheumatoid arthritis.

Coenzyme Q10: From bench to clinic in aging diseases, a translational review.

Coenzyme Q10 (CoQ10) is a ubiquitous molecule present in all eukaryotic organisms whose principal role in the cell is related to its participation in the electron transport chain in the inner mitochondrial membrane. CoQ10 plays a major role in the control of cell redox status, and both the amount and functionality of this molecule have been related to the regulation of reactive oxygen species generation. Numerous reports can be found discussing the implications of CoQ10 supplementation in human studies and clinical trials related to aging. However, few reviews have made an updating through the translational point of view to integrate both basic and clinical aspects. The aim of this paper is to review our current knowledge from CoQ10 implications at biochemical and physiological level, in order to unravel the molecular mechanisms involved in its application in clinical practice. Although the importance of CoQ10 has been mainly attributed to its role as an agent for energy transduction in mitochondria, new functions for CoQ10 have been described in the recent past years, including anti-inflammatory effects, gene expression regulation and lipid bilayer membranes stabilization, which explain its involvement in aging and age-related diseases such as cardiovascular diseases, renal failure and neurodegenerative diseases.

Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease.

The mechanisms of action of the dietary components of the Mediterranean diet are reviewed in prevention of cardiovascular disease, stroke, age-associated cognitive decline and Alzheimer disease. A companion article provides a comprehensive review of extra-virgin olive oil. The benefits of consumption of long-chain ω-3 fatty acids are described. Fresh fish provides eicosapentaenoic acid while α-linolenic acid is found in canola and soybean oils, purslane and nuts. These ω-3 fatty acids interact metabolically with ω-6 fatty acids mainly linoleic acid from corn oil, sunflower oil and peanut oil. Diets rich in ω-6 fatty acids inhibit the formation of healthier ω-3 fatty acids. The deleterious effects on lipid metabolism of excessive intake of carbohydrates, in particular high-fructose corn syrup and artificial sweeteners, are explained. The critical role of the ω-3 fatty acid docosahexaenoic acid in the developing and aging brain and in Alzheimer disease is addressed. Nutritional epidemiology studies, prospective population-based surveys, and clinical trials confirm the salutary effects of fish consumption on prevention of coronary artery disease, stroke and dementia. Recent recommendations on fish consumption by pregnant women and potential mercury toxicity are reviewed. The polyphenols and flavonoids of plant origin play a critical role in the Mediterranean diet, because of their antioxidant and anti-inflammatory properties of benefit in type-2 diabetes mellitus, cardiovascular disease, stroke and cancer prevention. Polyphenols from fruits and vegetables modulate tau hyperphosphorylation and beta amyloid aggregation in animal models of Alzheimer disease. From the public health viewpoint worldwide the daily consumption of fruits and vegetables has become the main tool for prevention of cardiovascular disease and stroke. We review the important dietary role of cereal grains in prevention of coronary disease and stroke. Polyphenols from grapes, wine and alcoholic beverages are discussed, in particular their effects on coagulation. The mechanisms of action of probiotics and vitamins are also included.

[Vitamin D and pediatrics respiratory diseases]. / Vitamina D y enfermedades respiratorias pediátricas.

The better understanding of the global activity of vitamin D has led to an intense search for its involvement in non-skeletal diseases. This article presents an updated review of the relationship between vitamin D and pediatric respiratory pathology. A literature search was performed in PUBMED using free terms and MESH terms: vitamin D, asthma, respiratory system diseases, and bronchiolitis. Stu dies in human patients younger than 18 years and animals, published in English and Spanish until 2017 were included. 507 articles were found, of which 43 were included. Indirect evidence suggests a role of vitamin D and fetal lung maturation. In relation to pediatric pulmonary pathology, studies are scarce and inconclusive. Recent meta-analyses performed with individualized evaluation of the participants shows an important protective role of vitamin D supplementation in the prevention of severe asthma exacerbations and acute viral infections. In bronchiolitis, the results are contradictory, with no clear relationship between plasma levels and severity. There is not enough evidence to assess the benefits of vitamin D supplementation in cystic fibrosis and tuberculosis. A direct relationship between the severity of sleep-related breathing disorders and vitamin D plasma levels has recently been proposed, although the exact mechanisms involved in this association are unknown. Current information suggests that vitamin D supplementation may represent a cost-effective strategy in redu cing important causes of infant morbidity and mortality.

Role of L-carnitine in female infertility.

BACKGROUND: L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC), have immense functional capabilities to regulate the oxidative and metabolic status of the female reproductive system. The vulnerability of this system to free radicals demand for advanced strategies to combat them. For this purpose, the 'quasi vitamins' LC and ALC can be used either individually, or in combination with each other or with other antioxidants. MAIN BODY: This review (a) summarizes the effects of carnitines on female fertility along with the findings from various in vivo and in vitro studies involving human, animal and assisted reproductive technology, and (b) proposes their mechanism of actions in improving female fertility through their integrated actions on reducing cellular stress, maintaining hormonal balance and enhancing energy production. They reportedly aid ß-oxidation in oocytes, maintain its cell membrane stability by acetylation of phospholipids and amphiphilic actions, prevent free radical-induced DNA damage and also stabilize acetyl Co-A/Co-A ratio for adequate acetyl storage as energy supply to maintain the robustness of reproductive cells. CONCLUSION: While both LC and ALC have their applications in improving female fertility, ALC is preferred for its better antioxidant properties and LC for amelioration of energy supply to the cells. These beneficial effects show great promise in its application as a treatment option for women facing infertility disorders.

Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction.

Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and autonomic dysfunction. However, more patient-centered trials on the use of vitamin D supplementation in different conditions are needed.

Small molecules, both dietary and endogenous, influence the onset of lens cataracts.

How the lens ages successfully is a lesson in biological adaption and the emergent properties of its complement of cells and proteins. This living tissue contains some of the oldest proteins in our bodies and yet they remain functional for decades, despite exposure to UV light, to reactive oxygen species and all the other hazards to protein function. This remarkable feat is achieved by a shrewd investment in very stable proteins as lens crystallins, by providing a reservoir of ATP-independent protein chaperones unequalled by any other tissue and by an oxidation-resistant environment. In addition, glutathione, a free radical scavenger, is present in mM concentrations and the plasma membranes contain oxidation-resistant sphingolipids what compromises lens function as it ages? In this review, we examine the role of small molecules in the prevention or causation of cataracts, including those associated with diet, metabolic pathways and drug therapy (steroids).

Vitamins for enhancing plant resistance.

MAIN CONCLUSION: This paper provides an overview on vitamins with inducing activities in plants, the molecular and cellular mechanisms implicated, and the hormonal signalling-network regulating this process. Moreover, it reports how vitamins might be part of the molecular events linked to induced resistance by the conventional elicitors. Induced resistance (IR), exploiting the plant innate-defense system is a sustainable strategy for plant disease control. In the last decade, vitamins have been proven to act as inducers of disease resistance, and these findings have received an important attention owing to their safety and cost effectiveness. Vitamins, including thiamine (TH, vitamin B1), riboflavin (RF, vitamin B2), menadione sodium bisulfite (MSB, vitamin K3), Para-aminobenzoic acid (PABA, vitamin Bx), and folic acid (FA, vitamin B9) provided an efficient protection against a wide range of pathogens through the modulation of specific host-defense facets. However, other vitamins, such as ascorbic acid (AA, vitamin C) and tocopherols (vitamin E), have been shown to be a part of the molecular mechanisms associated to IR. The present review is the first to summarize what vitamins are acting as inducers of disease resistance in plants and how could they be modulated by the conventional elicitors. Thus, this report provides an overview on the protective abilities of vitamins and the molecular and cellular mechanisms underlying their activities. Moreover, it describes the hormonal-signalling network regulating vitamin-signal transduction during IR. Finally, a biochemical model describing how vitamins are involved in the establishment of IR process is discussed.

Is There a Relationship between Nutrition, Facial Development, and Crowding of the Teeth?

Nutrition plays an important role, especially key vitamins D3 and K2 which are necessary for proper dentofacial development and food consistency influence on crowding and dental arches narrowing. Changes in our dentition and facial appearance are caused by changing our diet from primitive hunter gatherer to a more modern industrialized agriculture. Nutrition and its impact on epigeneticaly- mediated mechanisms continuously shape our phenotype which impacts overall health and can reverse the path for overall health and facial bone development. Orthodontics and nutrition both play a role in following nature's path to reestablishing facial balance and dental arches proportions to accommodate all 32 teeth.

MicroRNA-627 mediates the epigenetic mechanisms of vitamin D to suppress proliferation of human colorectal cancer cells and growth of xenograft tumors in mice.

BACKGROUND & AIMS: Vitamin D protects against colorectal cancer through unclear mechanisms. We investigated the effects of calcitriol (1α,25-dihydroxyvitamin D3; the active form of vitamin D) on levels of different microRNAs (miRNAs) in colorectal cancer cells from humans and xenograft tumors in mice. METHODS: Expression of miRNAs in colorectal cancer cell lines was examined using the Ambion mirVana miRNA Bioarray. The effects of calcitriol on expression of miR-627 and cell proliferation were determined by real-time polymerase chain reaction and WST-1 assay, respectively; growth of colorectal xenograft tumors was examined in nude mice. Real-time polymerase chain reaction was used to analyze levels of miR-627 in human colon adenocarcinoma samples and nontumor colon mucosa tissues (controls). RESULTS: In HT-29 cells, miR-627 was the only miRNA significantly up-regulated by calcitriol. Jumonji domain containing 1A (JMJD1A), which encodes a histone demethylase, was found to be a target of miR-627. By down-regulating JMJD1A, miR-627 increased methylation of histone H3K9 and suppressed expression of proliferative factors, such as growth and differentiation factor 15. Calcitriol induced expression of miR-627, which down-regulated JMJD1A and suppressed growth of xenograft tumors from HCT-116 cells in nude mice. Overexpression of miR-627 prevented proliferation of colorectal cancer cell lines in culture and growth of xenograft tumors in mice. Conversely, blocking the activity of miR-627 inhibited the tumor suppressive effects of calcitriol in cultured colorectal cancer cells and in mice. Levels of miR-627 were decreased in human colon adenocarcinoma samples compared with controls. CONCLUSIONS: miR-627 mediates tumor-suppressive epigenetic activities of vitamin D on colorectal cancer cells and xenograft tumors in mice. The messenger RNA that encodes the histone demethylase JMJD1A is a direct target of miR-627. Reagents designed to target JMJD1A or its messenger RNA, or increase the function of miR-627, might have the same antitumor activities of vitamin D without the hypercalcemic side effects.

Effects of vitamin D in skeletal muscle: falls, strength, athletic performance and insulin sensitivity.

Accompanying the high rates of vitamin D deficiency observed in many countries, there is increasing interest in the physiological functions of vitamin D. Vitamin D is recognized to exert extra-skeletal actions in addition to its classic roles in bone and mineral homeostasis. Here, we review the evidence for vitamin D's actions in muscle on the basis of observational studies, clinical trials and basic research. Numerous observational studies link vitamin D deficiency with muscle weakness and sarcopaenia. Randomized trials predominantly support an effect of vitamin D supplementation and the prevention of falls in older or institutionalized patients. Studies have also examined the effect of vitamin D in athletic performance, both inferentially by UV radiation and directly by vitamin D supplementation. Effects of vitamin D in muscle metabolic function, specifically insulin sensitivity, are also addressed in this review. At a mechanistic level, animal studies have evaluated the roles of vitamin D and associated minerals, calcium and phosphate, in muscle function. In vitro studies have identified molecular pathways by which vitamin D regulates muscle cell signalling and gene expression. This review evaluates evidence for the various roles of vitamin D in skeletal muscle and discusses controversies that have made this a dynamic field of research.

Re-evaluating the role of vitamin D in the periodontium.

The importance of vitamin D in maintaining skeletal health via the regulation of calcium has long been recognized as a critical function of this secosteroid. An abundance of literature shows an association between oral bone mineral density and some measure of systemic osteoporosis and suggests that osteoporosis/low bone mass may be a risk factor for periodontal disease. Recently, nonskeletal functions of vitamin D have gained notoriety for several reasons. Many cells that are not associated with calcium homeostasis have been demonstrated to possess membrane receptors for vitamin D. These include activated T and B lymphocytes, and skin, placenta, pancreas, prostate and colon cancer cells. In addition, vitamin D "insufficiency" is a worldwide epidemic and epidemiologic evidence has linked this condition to multiple chronic health problems, including cardiovascular and autoimmune diseases, hypertension and a variety of cancers. Interestingly, there is mounting evidence connecting diminished serum levels of vitamin D with increased gingival inflammation and supporting the concept of "continual vitamin D sufficiency" in maintaining periodontal health. The ability of vitamin D to regulate both the innate and the adaptive components of the host response may play an important role in this process. This review will examine the skeletal and nonskeletal functions of vitamin D, and explore its potential role in protecting the periodontium as well as in regulating periodontal wound healing.

There's life in the old dog yet: vitamin C as a therapeutic option in endothelial dysfunction.

The use of vitamin C against different diseases has been controversially and emotionally discussed since Linus Pauling published his cancer studies. In vitro and animal studies showed promising results and explained the impact of vitamin C, particularly in cases with endothelial dysfunction. Indeed, studies (reviewed in this issue of Critical Care by Oudemans-van Straaten and colleagues) using high-dose vitamin C and the parenteral route of application seem to be more successful than oral vitamin C delivery.

Vitamin C revisited.

This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis. Finally, high-dose vitamin C can augment antibacterial defense. These protective effects against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or burn seems to mitigate organ injury and dysfunction, and promote recovery after cardiac revascularization and in critically ill patients, in the latter partially in combination with other antioxidants. Of note, several questions remain to be solved, including optimal dose, timing and combination of vitamin C with other antioxidants. The combination obviously offers a synergistic effect and seems reasonable during sustained critical illness. High-dose vitamin C, however, provides a cheap, strong and multifaceted antioxidant, especially robust for resuscitation of the circulation. Vitamin C given as early as possible after the injurious event, or before if feasible, seems most effective. The latter could be considered at the start of cardiac surgery, organ transplant or major gastrointestinal surgery. Preoperative supplementation should consider the inhibiting effect of vitamin C on ischemic preconditioning. In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury.

Vitamins in dialysis: who, when and how much?

Despite the significant technical evolution of the blood purification methods, cardiovascular morbidity and mortality in dialysis patients is still several times higher than that observed in the general population. Vitamins are playing a crucial role in multiple key metabolic pathways. Due to multiple factors, dialysis patients present very often hypo- or hypervitaminosis for a broad range of vitamins. Dialysis in the context of renal replacement therapy is associated with a non-physiological potassium-sparing dietetic regime. Additionally, there is a non-selective intradialytic loss of micro- and macronutrients, deranged intracellular kinetics and gastrointestinal malabsorption due to uratemia. Frequent treatment with antibiotics due to infections associated with the acquired uremia-related immunosuppression may derange the vitamin-producing intestinal microflora. Certain agents prescribed in the context of renal failure or other conditions may reduce the absorption of vitamins from the gastrointestinal tract. These factors may deplete a dialysis patient from vitamins, especially the ones with antioxidant activity that may be associated with cardioprotective properties. In other cases, vitamins metabolized and excreted by the kidneys may be accumulated and exert toxic effects. The scope of this paper is to describe the main issues on vitamin therapy in dialysis patients in view of the ever contradictory opinions and practices.

The effect of nutrition on periodontal disease: a systematic review.

The link between nutrients and periodontal disease has not been clearly established. A PubMed and Cochrane database literature search was conducted. The published research reveals only a possible relationship between vitamins and minerals and periodontal disease. Vitamin E, zinc, lycopene and vitamin B complex may have useful adjunct benefits. However, there is inadequate evidence to link the nutritional status of the host to periodontal inflammation. More randomized controlled trials are needed to explore this association.

The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude.

BACKGROUND: Month of birth has previously been described as a risk factor for multiple sclerosis (MS). This has been hypothesised to be related to maternal vitamin D levels during pregnancy, although conclusive evidence to support this is lacking. To date, no large studies of latitudinal variation in the month of birth effect have been performed to advance this hypothesis. METHODS: Previously published data on month of birth from 151 978 MS patients were compared to expected birth rates. A linear regression model was used to assess the relationship between latitude and observed:expected birth ratio of MS patients for each month. RESULTS: Analysis of all reported data demonstrated a significant excess of MS risk in those born in April (observed:expected 1.05, p=0.05) and reduction in risk in those born in October (0.95, p=0.04) and November (0.92 p=0.01). A conservative analysis of 78 488 patients revealed an excess MS risk in those born in April (1.07, p=0.002) and May (1.11, p=0.0006), and a reduced risk in those born in October (ratio 0.94, p=0.004) and November (0.88, p=0.0002). A significant relationship between latitude and observed:expected ratio was demonstrated in December, and borderline significant relationships in May and August. CONCLUSIONS: Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude.

The role of vitamin D in chronic heart failure.

PURPOSE OF REVIEW: Despite advanced medical and device-based therapies, congestive heart failure (CHF) remains a major medical problem, associated with significant morbidity and mortality. Vitamin D deficiency is prevalent in CHF and is associated with poor outcomes. In this manuscript we review the evidence linking vitamin D deficiency and CHF and discuss potential mechanisms involved, as well the clinical data on vitamin D supplementation in CHF patients. RECENT FINDINGS: A clear relationship has been established between Vitamin D deficiency and increased mortality and morbidity in CHF. However, the mechanism involved is not clearly understood. Recent clinical and experimental evidence have identified the renin-angiotensin-aldosterone system and inflammatory cytokines as likely mediators that can lead to poor clinical outcomes via the cardiorenal syndrome. Clinical data on vitamin D supplementation also remain unestablished, with potential clinical benefits recently reported in patients with vitamin D deficiency. Nonetheless, large-scale randomized clinical trials are lacking. SUMMARY: Vitamin D is an emerging agent with tremendous potential and may represent a novel target for therapy in CHF. Further studies are needed to identify the mechanism(s) involved in the pathophysiology as well as to adequately examine the role of Vitamin D measurement and supplementation in patients with CHF.

Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement.

• The recommended level for serum 25-hydroxyvitamin D (25(OH)D) in infants, children, adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10-20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring. • Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation, assuming minimal sun exposure. • Risk factors for low vitamin D are: lack of skin exposure to sunlight, dark skin, southerly latitude, conditions affecting vitamin D metabolism and storage (including obesity) and, for infants, being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor. • Targeted measurement of 25(OH)D levels is recommended for infants, children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit. • Vitamin D deficiency can be treated with daily low-dose vitamin D supplements, although barriers to adherence have been identified. High-dose intermittent vitamin D can be used in children and adolescents. Treatment should be paired with health education and advice about sensible sun exposure. Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D3 daily for at least the first year of life. • There is increasing evidence of an association between low vitamin D and a range of non-bone health outcomes, however there is a lack of data from robust randomised controlled trials of vitamin D supplementation.