Retinal changes associated with multivitamin deficiency before and after supplementation.

BACKGROUND: Nutritional visual defects are apparently uncommon nowadays in developed nations. Retinal change-related visual defects caused by hypovitaminoses may be underdiagnosed. AIM OF THE STUDY: To investigate the retinal structural and functional changes in a patient with multivitamin deficiency before and during vitamin supplementation. METHODS: A 51-year-old female had been on vegetarian diet as a child, and on restrict vegan diet during the last 2 years, developing severe bilateral deterioration of visual function and polyneuropathy. Blood test revealed low levels of vitamin A, B6 and D. The patient underwent examinations with optical coherence tomography (OCT), computerized visual field examination (VF), electroretinography (ERG), visual evoked potentials (VEP) and neurography before and after vitamin supplementation. RESULTS: Visual acuity (VA) was 20/1000 and VF examination showed central scotoma in both eyes. Color vision was significantly affected. Full-field ERG showed normal rod and cone function, but a clearly reduced central peak was registered in multifocal ERG (mf-ERG), indicating impaired fovea function. VEP showed delayed latency and low amplitude of P100 in both eyes. Neurography showed sensory polyneuropathy. OCT showed significant thinning of macular ganglion cell plus inner plexiform layer (GCIPL) with rapid progression. Retinal nerve fiber layer (RNFL) was preserved and normal, which is in contrast to neuroinflammatory conditions. After 2.5 years of multivitamin supplementation, the visual functions were improved. GCIPL thickness was stable without further deterioration. CONCLUSIONS: Multivitamin deficiency results in progressive thinning of GCIPL with severe visual deterioration. In contrast to neuroinflammation, RNFL is preserved and normal. Stabilized GCIPL during vitamin supplementation was associated with improved visual function. OCT provides a sensitive and objective measure for differential diagnosis, monitoring retinal change and response to therapy.

Update on Biotin Therapy in Dermatology: Time for a Change.

Biotin (vitamin B7 or H) is found in milk, nuts, egg yolks, cereals, supplements, synthesized by intestinal bacteria, and is required for gluconeogenesis, fatty acid synthesis and amino acid catabolism.

Metabolic Consequences of Supplemented Methionine in a Clinical Context.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease. This review discusses the evidence generated in preclinical and clinical studies on the importance and potentially harmful effects of Met supplementation and elaborates on potential clinical applications of supplemental Met with reference to clinical studies performed over the past 20 y. Recently acquired knowledge about the NOAEL (no observed adverse effect level) of 46.3 mg · kg-1 · d-1 and the LOAEL (lowest observed adverse effect level) of 91 mg · kg-1 · d-1 of supplemented Met will guide the design of future studies to further establish the role of Met as a potential (safe) candidate for nutritional supplementation in clinical applications.

Vitamin D deficiency exacerbates bleomycin-induced pulmonary fibrosis partially through aggravating TGF-ß/Smad2/3-mediated epithelial-mesenchymal transition.

BACKGROUND: Our earlier report indicated that active vitamin D3 inhibited epithelial-mesenchymal transition (EMT) in bleomycin (BLM)-induced pulmonary fibrosis. The objective of this study was to further investigate whether vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis. METHODS: This study consists of two independent experiments. Experiment 1, male mice were fed with vitamin D deficient (VDD) fodder. Experiment 2, Cyp27b1+/+, Cyp27b1+/- and Cyp27b1-/- mice were fed with standard diet. For pulmonary fibrosis, mice were intratracheally instilled with a single dose of BLM (1.5 mg/kg). Serum 25(OH) D level was measured. Pulmonary collagen deposition was assessed by Sirius red staining. EMT was measured and transforming growth factor-beta (TGF-ß)/Smad3 signaling was evaluated in the lungs of BLM-treated mice. RESULTS: The relative weight of lungs was elevated in BLM-treated mice. Col1α1 and Col1α2, two collagen protein genes, were upregulated, and collagen deposition, as determined by Sirius red staining, was observed in the lungs of BLM-treated mice. E-cadherin, an epithelial marker, was downregulated. By contrast, vimentin and α-SMA, two EMT markers, were upregulated in the lungs of BLM-treated mice. Pulmonary TGF-ß/Smad3 signaling was activated in BLM-induced lung fibrosis. Further analysis showed that feeding VDD diet, leading to vitamin D deficiency, aggravated elevation of BLM-induced relative lung weight. Moreover, feeding VDD diet aggravated BLM-induced TGF-ß/Smad3 activation and subsequent EMT in the lungs. In addition, feeding VDD diet exacerbated BLM-induced pulmonary fibrosis. Additional experiment showed that Cyp27b1 gene knockout, leading to active vitamin D3 deficiency, exacerbated BLM-induced pulmonary fibrosis. Moreover, Cyp27b1 gene knockout aggravated pulmonary TGF-ß/Smad2/3 activation and subsequent EMT in BLM-induced lung fibrosis. CONCLUSION: Vitamin D deficiency exacerbates BLM-induced pulmonary fibrosis partially through aggravating TGF-ß/Smad2/3-mediated EMT in the lungs.

Multiple vitamin deficiencies additively increase the risk of incident fractures in Japanese postmenopausal women.

The associations of multiple vitamin deficiencies on incident fractures were uncertain, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. The number of deficiencies was additively associated with incident fracture after adjustment for possible confounding factors including the treatment of osteoporosis. INTRODUCTION: To evaluate the associations of multiple vitamin deficiencies on incident fractures, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. METHODS: This analysis used a subset of the ongoing cohort maintained by a primary care institution. Inclusion criteria of the present study were postmenopausal women aged ≥ 50 years, without vitamin supplementation and secondary osteoporosis. Baseline serum concentrations of 25-hydroxyvitamin D (25(OH)D), undercarboxylated osteocalcin (ucOC), and homocysteine (Hcy) were measured to assess vitamin D, vitamin K, and vitamin B, respectively. Since 25(OH) D positively relates to vitamin D, ucOC and Hcy negatively relate to vitamin K and vitamin B nutrients, respectively, the subjects with lower (25(OH)D) or higher (ucOC or Hcy) values than each median value was defined as subjects with the corresponding vitamin deficiency. Subjects were divided into four groups according to the number of deficiency: no deficiency, single deficiency, double deficiencies, and triple deficiencies. Relationships between the vitamin deficiencies and incident fractures were evaluated by Cox regression analysis. RESULTS: A total of 889 subjects were included in this analysis; their mean and SD age was 68.3 ± 9.5 years, and the follow-up period was 6.3 ± 5.1 years. The numbers of subjects in the four groups were 139 (15.6%), 304 (34.2%), 316 (35.5%), and 130 (14.6%) for the groups with no, single, double, and triple deficiencies, respectively. Incident fractures were observed in 264 subjects (29.7%) during the observation period. The number of deficiencies was significantly associated with incident fracture (hazard ratio 1.25, 95% confidence interval 1.04-1.50, P = 0.018) after adjustment for possible confounding factors including the treatment of osteoporosis. CONCLUSION: Accumulation of vitamin deficiencies was related to incident fractures.

[Neurological pathology associated with vitamin B group deficiency: thiamine, folate and cobalamin]. / Patología neurológica por déficit de vitaminas del grupo B: tiamina, folato y cobalamina.

The "fragility" of the nervous system, especially concerning to its nutrition and metabolism, explains why vitamin deficits are an important cause of neurological pathology. Some deficiency diseases, which can be very severe and irreversible, are still present in our environment; diagnosis, which must be early so as not to delay treatment, can be difficult if we do not have them in mind. In this review we address the most relevant neurological diseases associated with thiamine, folate and cobalamin deficiency, and we focus especially combined subacute degeneration and Wernicke-Korsakoff syndrome.

La "fragilidad" del sistema nervioso, en especial en lo referente a su nutrición y metabolismo, explica que los déficits vitamínicos sean una causa importante de patología neurológica. Algunas enfermedades carenciales, que pueden ser muy graves e irreversibles, aún se presentan en nuestro entorno. Su diagnóstico, que debe ser precoz para no retrasar el tratamiento, puede ser complicado si no las tenemos en mente. En esta revisión abordamos las enfermedades neurológicas más relevantes asociadas al déficit de tiamina, folatos y cobalamina, deteniéndonos especialmenteen la degeneración combinada subaguda y el síndrome de Wernicke-Korsakoff.

Patología neurológica por déficit de vitaminas del grupo B: tiamina, folato y cobalamina / Neurological pathology associated with vitamin B group deficiency: thiamine, folate and cobalamin

La "fragilidad" del sistema nervioso, en especial en lo referente a su nutrición y metabolismo, explica que los déficits vitamínicos sean una causa importante de patología neurológica. Algunas enfermedades carenciales, que pueden ser muy graves e irreversibles, aún se presentan en nuestro entorno. Su diagnóstico, que debe ser precoz para no retrasar el tratamiento, puede ser complicado si no las tenemos en mente. En esta revisión abordamos las enfermedades neurológicas más relevantes asociadas al déficit de tiamina, folatos y cobalamina, deteniéndonos especialmente en la degeneración combinada subaguda y el síndrome de Wernicke-Korsakoff

The "fragility" of the nervous system, especially concerning to its nutrition and metabolism, explains why vitamin deficits are an important cause of neurological pathology. Some deficiency diseases, which can be very severe and irreversible, are still present in our environment; diagnosis, which must be early so as not to delay treatment, can be difficult if we do not have them in mind. In this review we address the most relevant neurological diseases associated with thiamine, folate and cobalamin deficiency, and we focus especially combined subacute degeneration and Wernicke-Korsakoff syndrome

Selected B vitamins and their possible link to the aetiology of age-related sarcopenia: relevance of UK dietary recommendations.

The possible roles of selected B vitamins in the development and progression of sarcopenia are reviewed. Age-related declines in muscle mass and function are associated with huge and increasing costs to healthcare providers. Falls and loss of mobility and independence due to declining muscle mass/function are associated with poor clinical outcomes and their prevention and management are attractive research targets. Nutritional status appears a key modifiable and affordable intervention. There is emerging evidence of sarcopenia being the result not only of diminished anabolic activity but also of declining neurological integrity in older age, which is emerging as an important aspect of the development of age-related decline in muscle mass/function. In this connection, several B vitamins can be viewed as not only cofactors in muscle synthetic processes, but also as neurotrophic agents with involvements in both bioenergetic and trophic pathways. The B vitamins thus selected are examined with respect to their relevance to multiple aspects of neuromuscular function and evidence is considered that requirements, intakes or absorption may be altered in the elderly. In addition, the evidence base for recommended intakes (UK recommended daily allowance) is examined with particular reference to original datasets and their relevance to older individuals. It is possible that inconsistencies in the literature with respect to the nutritional management of sarcopenia may, in part at least, be the result of compromised micronutrient status in some study participants. It is suggested that in order, for example, for intervention with amino acids to be successful, underlying micronutrient deficiencies must first be addressed/eliminated.

Organ Co-Relationship in Tryptophan Metabolism and Factors That Govern the Biosynthesis of Nicotinamide from Tryptophan.

The pathway of tryptophan (Trp)-nicotinamide is very important nutritionally because a vitamin nicotinamide is biosynthesized from an amino acid Trp. Until we started studying the factors that affect the Trp-nicotinamide conversion rate, little data existed. Data obtained from TDO (Trp 2,3-dioxygenase)-KO (knock-out) mice have revealed that mice can biosynthesize a necessary amount of nicotinamide from Trp by indoleamine 2,3-dioxygenase (IDO) even when TDO is lacking. It has also been shown that 3-hydroxyanthranilic acid is a key intermediate. Urine upper metabolites such as kynurenic acid and xanthurenic acid originate from non-hepatic tissues but not from the liver. Data obtained from quinolinic acid phosphoribosyltransferase (QPRT)-KO mice indicated that the Trp→quinolinic acid conversion ratio was 6%. Urine quinolinic acid levels and the conversion ratio of Trp to nicotinamide were the same between hetero and wild mice. These findings indicate that QPRT is not the rate-limiting enzyme in the conversion. Thus, the limiting factors in the conversion of Trp to nicotinamide are the amounts of 3-hydroxyanthranilic acid and quinolinic acid in the liver and the activity of liver 3-hydroxyanthranilic acid 3,4-dioxygenase. Studies on factors have shown that conversion of Trp to nicotinamide is increased by adequate intake of good quality protein, and adequate intake of unsaturated fatty acids and starch. However, conversion was decreased by deficient niacin, vitamin B2, or vitamin B6, excessive intake of protein, saturated fatty acids, or glucose and fructose, or intake of protein with low Trp content, and insufficient mineral intake.

B Vitamins and Ageing.

Vitamin B contributes to the overall health and wellbeing, including that of energy metabolism, methylation, synthesis and DNA repair and proper immune function. Deficiency in B vitamins has been linked to neurocognitive disorders, mitochondrial dysfunction, immune dysfunction and inflammatory conditions. In ageing populations B vitamin deficiency has been linked to cardiovascular disorders, cognitive dysfunction, osteoporosis and methylation disorders and can increase the risk of developing degenerative diseases, particularly cardiovascular disease, cognitive diseases and osteoporosis. Optimization of B vitamin status in the elderly may prove beneficial in the prevention of degenerative diseases. Here we discuss broadly the role of B vitamins in ageing.

Metabolomic Evaluation of the Consequences of Plasma Cystathionine Elevation in Adults with Stable Angina Pectoris.

Background: An elevated circulating cystathionine concentration, which arises in part from insufficiencies of vitamin B-6, B-12, or folate, has been shown to be associated with cardiovascular disease (CVD) risk. Hydrogen sulfide (H2S) is a gasotransmitter involved in vasodilation, neuromodulation, and inflammation. Most endogenously produced H2S is formed by pyridoxal phosphate (PLP)-dependent enzymes by noncanonical reactions of the transsulfuration pathway that yield H2S concurrently form lanthionine and homolanthionine. Thus, plasma lanthionine and homolanthionine concentrations can provide relative information about H2S production in vivo.Objective: To determine the metabolic consequences of an elevated plasma cystathionine concentration in adults with stable angina pectoris (SAP), we conducted both targeted and untargeted metabolomic analyses.Methods: We conducted NMR and LC-mass spectrometry (MS) metabolomic analyses on a subset of 80 plasma samples from the Western Norway Coronary Angiography Cohort and selected, based on plasma cystathionine concentrations, a group with high cystathionine concentrations [1.32 ± 0.60 µmol/L (mean ± SD); n = 40] and a group with low cystathionine concentrations [0.137 ± 0.011 µmol/L (mean ± SD); n = 40]. Targeted and untargeted metabolomic analyses were performed and assessed with the use of Student's t tests corrected for multiple testing. Overall differences between the cystathionine groups were assessed by untargeted NMR and LC-MS metabolomic methods and evaluated by partial least squares discriminant analysis (PLS-DA) with significant discriminating metabolites identified with 99% confidence.Results: Subjects with high cystathionine concentrations had 75% higher plasma lanthionine concentrations (0.12 ± 0.044 µmol/L) than subjects with low cystathionine concentrations [0.032 ± 0.013 µmol/L (P < 0.001)]. Although plasma homolanthionine concentrations were notably higher than lanthionine concentrations, they were not different between the groups (P = 0.47). PLS-DA results showed that a high plasma cystathionine concentration in SAP was associated with higher glucose, branched-chain amino acids, and phenylalanine concentrations, lower kidney function, and lower glutathione and plasma PLP concentrations due to greater catabolism. The high-cystathionine group had a greater proportion of subjects in the postprandial state.Conclusion: These data suggest that metabolic perturbations consistent with higher CVD risk exist in SAP patients with elevated plasma cystathionine concentrations.

Alcoholic Pellagra as a Cause of Altered Mental Status in the Emergency Department.

BACKGROUND: Pellagra, which is caused by a deficiency of niacin and tryptophan, the precursor of niacin, is a rare disease in developed countries where alcoholism is a major risk factor due to malnutrition and lack of B vitamins. Although pellagra involves treatable dementia and psychosis, it is often underdiagnosed, especially in developed countries. CASE REPORT: In Japan, a 37-year-old man presented to the emergency department with altered mental status and seizures. Wernicke encephalopathy and alcohol withdrawal were suspected. The patient was treated with multivitamins, which did not include nicotinic acid amide, and oral diazepam. Despite medical treatment, his cognitive impairment progressively worsened, and eventually, pellagra was suspected. His response to treatment with nicotinic acid amide was substantial, and he was discharged without any long-term sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often underdiagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic.

Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer's phenotype.

Environmental and genetic risk factors are implicated in the pathogenesis of Alzheimer's disease (AD). However, how they interact and influence its pathogenesis remains to be investigated. High level of homocysteine (Hcy) is an AD risk factor and associates with an up-regulation of the ALOX5 gene. In the current paper we investigated whether this activation is responsible for the Hcy effect on the AD phenotype and the mechanisms involved. Triple transgenic mice were randomized to receive regular chow diet, a diet deficient in folate and B vitamins (Diet), which results in high Hcy, or the Diet plus zileuton, a specific ALOX5 inhibitor, for 7 months. Compared with controls, Diet-fed mice had a significant increase in Hcy levels, memory and learning deficits, up-regulation of the ALOX5 pathway, increased Aß levels, tau phosphorylation, and synaptic pathology, which were absent in mice treated with zileuton. In vivo and vitro studies demonstrated that the mechanism responsible was the hypomethylation of the ALOX5 promoter. Our findings demonstrate that the up-regulation of the ALOX5 is responsible for the Hcy-dependent worsening of the AD phenotype in a relevant mouse model of the disease. The discovery of this previously unknown cross-talk between these two pathways could afford novel therapeutic opportunities for treating or halting AD.

The effects of vitamin B on the immune/cytokine network and their involvement in depression.

Increasing evidence indicates that there are various interactions between the nervous system and the immune system, and that the immune system plays an important role in the pathogenesis of depression. Pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α) have been implicated in the neurobiological manifestations of depression. The immune/cytokine network has a powerful influence on the brain. In addition, deficiency in B vitamins has been linked to depression. Hence, greater knowledge of how immune cells change in the presence of vitamin B derivatives could improve understanding of how immune changes may correlate with depression, all of which are discussed herein.

FR - Nuevas indicaciones de nicotinamida en dermatología / Nicotinamide: new Indications in dermatology

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Obesity, related diseases and their relationship with vitamin D deficiency in adolescents.

INTRODUCTION: The rise in prevalence of obesity has occurred concomitantly to that of vitamin D deficiency (VDD). The aim of this narrative review was to describe the relationship between obesity and such related diseases as VDD in adolescents, in an effort to warn of the risks of this deficiency during this period of growth and development. METHODS: We searched the electronic databases PubMed, Medline, Scielo, Science Direct and Lilacs for articles from between 2000 and 2015 on the topics obesity and obesity-related diseases and VDD in adolescents. We included articles written in English, Spanish and Portuguese of the analytical variety (transverse and longitudinal), systematic reviews, meta-analysis and controlled clinical trials on humans, and excluded studies that were done on animals, inconclusive or with undefined methodology. RESULTS: We produced an overview of VDD in obesity, in cardiovascular diseases, in diabetes mellitus, in systemic hypertension, and in dyslipidemia. The prevalence of VDD was considered high in obese adolescents and their relationship with the obesity and related diseases was found in adolescents. These findings forewarn of possible clinical repercussions in the health of the adolescents, foremost because of how essential vitamin D is to growth and development, and for its interaction with obesity and obesity-related diseases. CONCLUSION: The worldwide rise in the obesity rate alongside the progressively increasing of vitamin D deficiency in adolescents is alarming. This relationship of VDD with the obesity and related diseases was found in adolescents. Vitamin D supplementation is considered promising measure to take with obese adolescents.

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health.

One carbon metabolism or methyl transfer, a crucial component of metabolism in all cells and tissues, supports the critical function of synthesis of purines, thymidylate and methylation via multiple methyl transferases driven by the ubiquitous methyl donor s-adenosylmethionine. Serine is the primary methyl donor to the one carbon pool. Intracellular folates and methionine metabolism are the critical components of one carbon transfer. Methionine metabolism requires vitamin B12, B6 as cofactors and is modulated by endocrine signals and is responsive to nutrient intake. Perturbations in one carbon transfer can have profound effects on cell proliferation, growth and function. Epidemiological studies in humans and experimental model have established a strong relationship between impaired fetal growth and the immediate and long term consequences to the health of the offspring. It is speculated that during development, maternal environmental and nutrient influences by their effects on one carbon transfer can impact the health of the mother, impair growth and reprogram metabolism of the fetus, and cause long term morbidity in the offspring. The potential for such effects is underscored by the unique responses in methionine metabolism in the human mother during pregnancy, the absence of transsulfuration activity in the fetus, ontogeny of methionine metabolism in the placenta and the unique metabolism of serine and glycine in the fetus. Dietary protein restriction in animals and marginal protein intake in humans causes characteristic changes in one carbon metabolism. The impact of perturbations in one carbon metabolism on the health of the mother during pregnancy, on fetal growth and the neonate are discussed and their possible mechanism explored.