Showing papers on "B vitamins published in 2011"

Choline and betaine in health and disease.

Abstract: Choline is an essential nutrient, but is also formed by de novo synthesis. Choline and its derivatives serve as components of structural lipoproteins, blood and membrane lipids, and as a precursor of the neurotransmitter acetylcholine. Pre-and postnatal choline availability is important for neurodevelopment in rodents. Choline is oxidized to betaine that serves as an osmoregulator and is a substrate in the betaine–homocysteine methyltransferase reaction, which links choline and betaine to the folate-dependent one-carbon metabolism. Choline and betaine are important sources of one-carbon units, in particular, during folate deficiency. Choline or betaine supplementation in humans reduces concentration of total homocysteine (tHcy), and plasma betaine is a strong predictor of plasma tHcy in individuals with low plasma concentration of folate and other B vitamins (B2, B6, and B12) in combination TT genotype of the methylenetetrahydrofolate reductase 677 C->T polymorphism. The link to one-carbon metabolism and the recent availability of food composition data have motivated studies on choline and betaine as risk factors of chronic diseases previously studied in relation to folate and homocysteine status. High intake and plasma level of choline in the mother seems to afford reduced risk of neural tube defects. Intake of choline and betaine shows no consistent relation to cancer or cardiovascular risk or risk factors, whereas an unfavorable cardiovascular risk factor profile was associated with high choline and low betaine concentrations in plasma. Thus, choline and betaine showed opposite relations with key components of metabolic syndrome, suggesting a disruption of mitochondrial choline oxidation to betaine as part of the mitochondrial dysfunction in metabolic syndrome.

Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis

Abstract: Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response

Abstract: Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in regenerating nicotinamide adenine dinucleotide (NAD(+)) from nicotinamide in mammals. NAMPT has crucial roles for many cellular functions by regulating NAD(+)-dependent SIRT1 deacetylase. However, roles of NAMPT in cancer are poorly defined. In this study, we show that NAMPT is prominently overexpressed in human prostate cancer cells along with SIRT1. Elevation of NAMPT expression occurs early for the prostate neoplasia. Inhibition of NAMPT significantly suppresses cell growth in culture, soft agar colony formation, cell invasion and growth of xenografted prostate cancer cells in mice. NAMPT knockdown sensitizes prostate cancer cells to oxidative stress caused by H(2)O(2) or chemotherapeutic treatment. Overexpression of NAMPT increases prostate cancer cell resistance to oxidative stress, which is partially blocked by SIRT1 knockdown. We demonstrate that in addition to modulating SIRT1 functions, the NAMPT inhibition reduces forkhead box, class 'O' (FOXO)3a protein expression and its downstream anti-oxidant genes catalase and manganese superoxide dismutase. Our results suggest important roles of concomitant upregulation of NAMPT and SIRT1 along with increased FOXO3a protein level for prostate carcinogenesis and their contribution to oxidative stress resistance of prostate cancer cells. These findings may have implications for exploring the NAMPT pathway for prostate cancer prevention and treatment.

Deficiency in myeloid differentiation factor-2 and toll-like receptor 4 expression attenuates nonalcoholic steatohepatitis and fibrosis in mice.

Abstract: Toll-like receptor 4 (TLR4) and its coreceptor, myeloid differentiation factor-2 (MD-2), are key in recognition of lipopolysaccharide (LPS) and activation of proinflammatory pathways. Here we tested the hypothesis that TLR4 and its coreceptor MD-2 play a central role in nonalcoholic steatohepatitis (NASH) and liver fibrosis in nonalcoholic fatty liver disease. Mice of control genotypes and those deficient in MD-2 or TLR4 [knockout (KO)] received methionine choline-deficient (MCD) or methionine choline-supplemented (MCS) diet. In mice of control genotypes, MCD diet resulted in NASH, liver triglycerides accumulation, and increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, compared with MCS diet. These features of NASH were significantly attenuated in MD-2 KO and TLR4 KO mice. Serum alanine aminotransferase, an indicator of liver injury, was increased in MCD diet-fed genotype controls but was attenuated in MD-2 KO and TLR4 KO mice. Inflammatory activation, indicated by serum TNF-α and nictoinamide adenine dinucleotide phosphate oxidase complex mRNA expression and activation, was significantly lower in MCD diet-fed MD-2 KO and TLR4 KO compared with corresponding genotype control mice. Markers of liver fibrosis [collagen by Sirius red and α-smooth muscle actin (SMA) staining, procollagen-I, transforming growth factor-β1, α-SMA, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1 mRNA] were attenuated in MD-2 and TLR4 KO compared with their control genotype counterparts. In conclusion, our results demonstrate a novel, critical role for LPS recognition complex, including MD-2 and TLR4, through NADPH activation in liver steatosis, and fibrosis in a NASH model in mice.

TGF-β regulates Nox4, MnSOD and catalase expression, and IL-6 release in airway smooth muscle cells

Abstract: Reactive oxygen species (ROS) are generated as a result of normal cellular metabolism, mainly through the mitochondria and peroxisomes, but their release is enhanced by the activation of oxidant enzymes such as NADPH oxidases or downregulation of endogenous antioxidant enzymes such as manganese-superoxide dismutase (MnSOD) and catalase. Transforming growth factor-β (TGF-β), found to be overexpressed in airway smooth muscle (ASM) from asthmatic and chronic obstructive pulmonary disease patients, may be a pivotal regulator of abnormal ASM cell (ASMC) function in these diseases. An important effect of TGF-β on ASMC inflammatory responses is the induction of IL-6 release. TGF-β also triggers intracellular ROS release in ASMCs by upregulation of NADPH oxidase 4 (Nox4). However, the effect of TGF-β on the expression of key antioxidant enzymes and subsequently on oxidant/antioxidant balance is unknown. Moreover, the role of redox-dependent pathways in the mediation of the proinflammatory effects of TGF-β in ASMCs is unclear. In this study, we show that TGF-β induced the expression of Nox4 while at the same time inhibiting the expression of MnSOD and catalase. This change in oxidant/antioxidant enzymes was accompanied by elevated ROS levels and IL-6 release. Further studies revealed a role for Smad3 and phosphatidyl-inositol kinase-mediated pathways in the induction of oxidant/antioxidant imbalance and IL-6 release. The changes in oxidant/antioxidant enzymes and IL-6 release were reversed by the antioxidants N-acetyl-cysteine (NAC) and ebselen through inhibition of Smad3 phosphorylation, indicating redox-dependent activation of Smad3 by TGF-β. Moreover, these findings suggest a potential role for NAC in preventing TGF-β-mediated pro-oxidant and proinflammatory responses in ASMCs. Knockdown of Nox4 using small interfering RNA partially prevented the inhibition of MnSOD but had no effect on catalase and IL-6 expression. These findings provide novel insights into redox regulation of ASM function by TGF-β.

Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans

Abstract: Aims/hypothesis Nicotinamide phosphoribosyltransferase (NAMPT) is a multifunctional protein potentially involved in obesity and glucose metabolism. We systematically studied the association between circulating NAMPT, obesity, interventions and glucose metabolism and investigated potential underlying inflammatory mechanisms.

Antiepileptic drugs interact with folate and vitamin B12 serum levels.

Abstract: OBJECTIVE: Antiepileptic drugs (AEDs) are important for the treatment of epilepsy, psychiatric diseases, and pain syndromes. Small studies have suggested that AED treatment reduces serum levels of folate and vitamin B12. METHODS: This prospective monocenter study aimed at testing the hypothesis that AED treatment is associated with folate and vitamin B12 serum levels in a large population. A total of 2730 AED-treated and 170 untreated patients with epilepsy and 200 healthy individuals were enrolled. RESULTS: Treatment with carbamazepine, gabapentin, oxcarbazepine, phenytoin, primidone, or valproate was associated with lower mean serum folate levels or with a higher frequency of folate levels below the reference range in comparison with the entire group of patients, untreated patients, or controls. Treatment with phenobarbital, pregabalin, primidone, or topiramate was associated with lower vitamin B12 levels compared with the entire group of patients. Vitamin B12 serum levels were higher in patients treated with valproate compared with the entire group of patients, untreated patients, and healthy controls. Folate or vitamin B12 levels below the reference range were associated with higher mean corpuscular volume (MCV) and higher homocysteine plasma levels. Vitamin substitution for 3 months in 141 patients with folate or vitamin B12 levels below the reference range yielded normal vitamin levels in 95% of the supplemented patients and reduced MCV and homocysteine plasma levels. INTERPRETATION: Treatment with most of the commonly used AEDs is associated with reduced folate or vitamin B12 serum levels and is a risk factor for hyperhomocysteinemia. Oral substitution is effective to restore vitamin, MCV, and homocysteine levels. Ann Neurol 2011;

Homocysteine: a biomarker in neurodegenerative diseases.

Abstract: Diseases of the central nervous system are found in patients with severe hyperhomocysteinemia (HHcy). Epidemiological studies show a positive, dose-dependent relationship between mild-to-moderate increases in plasma total homocysteine concentrations (Hcy) and the risk of neurodegenerative diseases, such as Alzheimer's disease, vascular dementia, cognitive impairment or stroke. HHcy is a surrogate marker for B vitamin deficiency (folate, B12, B6) and a neurotoxic agent. The concept of improving the patient's clinical outcome by lowering of Hcy with B vitamins seems to be attractive. Recent B vitamin supplementation trials demonstrated a slowing of brain atrophy and improvement in some domains of cognitive function. Meta-analysis of secondary prevention trials showed that B vitamins supplementation caused a decrease in plasma Hcy and a trend for lowering the risk of stroke. HHcy is common in elderly people. Therefore, it seems prudent to identify B vitamin deficient subjects and to ensure sufficient vitamin intake. Therefore, recent evidence supports the role of Hcy as a potential biomarker in age-related neurodegenerative diseases.

Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene.

Abstract: Mitochondrial complex I deficiency is the most common oxidative phosphorylation defect. Mutations have been detected in mitochondrial and nuclear genes, but the genetics of many patients remain unresolved and new genes are probably involved. In a consanguineous family, patients presented easy fatigability, exercise intolerance and lactic acidosis in blood from early childhood. In muscle, subsarcolemmal mitochondrial proliferation and a severe complex I deficiency were observed. Exercise intolerance and complex I activity was improved by a supplement of riboflavin at high dosage. Homozygosity mapping revealed a candidate region on chromosome three containing six mitochondria-related genes. Four genes were screened for mutations and a homozygous substitution was identified in ACAD9 (c.1594 C>T), changing the highly conserved arginine-532 into tryptophan. This mutation was absent in 188 ethnically matched controls. Protein modelling suggested a functional effect due to the loss of a stabilizing hydrogen bond in an α-helix and a local flexibility change. To test whether the ACAD9 mutation caused the complex I deficiency, we transduced fibroblasts of patients with wild-type and mutant ACAD9. Wild-type, but not mutant, ACAD9 restored complex I activity. An unrelated patient with the same phenotype was compound heterozygous for c.380 G>A and c.1405 C>T, changing arginine-127 into glutamine and arginine-469 into tryptophan, respectively. These amino acids were highly conserved and the substitutions were not present in controls, making them very probably pathogenic. Our data support a new function for ACAD9 in complex I function, making this gene an important new candidate for patients with complex I deficiency, which could be improved by riboflavin treatment.

Relationship of folate, vitamin B12 and methylation of insulin-like growth factor-II in maternal and cord blood

Abstract: Relationship of folate, vitamin B 12 and methylation of insulin-like growth factor-II in maternal and cord blood

A Potential Design Flaw of Randomized Trials of Vitamin Supplements

Abstract: What are scientists, physicians, and the general public to make of the many null findings from randomized controlled trials (RCTs) of vitamin supplements? These trials are usually conducted on the basis of positive findings from prospective epidemiological studies and laboratory evidence of biological mechanisms. A common view is that the negative findings from the RCTs offer incontrovertible evidence that the nutrient is unrelated to disease and that the epidemiological studies are biased. An alternative explanation is that most RCTs of vitamin supplements are designed to test the hypothesis that supplementation, no matter the nutrient status, is protective. Vitamin treatment may not be effective in these trials because nutrient intake among the participants is already at optimum levels. To specify, examples are provided from the field of dementia and investigations of 3 dietary components: vitamin E, B vitamins, and docosahexaenoic acid. A basic principle of nutrition is that most nutrients have a nonlinear, inverted U-shaped association with optimum physiological function (Figure). Very low nutrient levels in diet or tissues result in poor function or even death. As the nutrient level increases, function also increases. Optimal functioning occurs over a fairly wide range of nutrient levels but at some point, higher levels become toxic and result in suboptimum function. Figure Relationship Between Level of Nutrient Status and Physiological Function Consideration of nutrient level is critically important in the assessment of the epidemiological evidence. For example, among the first 3 prospective epidemiological studies1–3 reporting on the association of dietary antioxidants and the risk of Alzheimer disease, 2 studies found inverse associations with vitamin E from food sources1,2 and 1 found no association.3 Close examination of the reported intake levels of these study populations revealed that vitamin E intake was very low in the study with null findings, and the median intake level of the highest quartile of 4.7 mg per day was in the lowest categories of intake in the other 2 studies (lowest tertile <10.5 mg/d1 and quintile median of 4.2 mg/d2). Thus, a plausible explanation for the null association is that the range of vitamin intake in this study population was below the level of protective benefit to observe an association. Nutrient levels are rarely considered in trial inclusion criteria. Further, trial volunteers are typically healthy behavior–seeking individuals and are unlikely to have low nutrient intake. More probably, intake levels are already at the level for optimal functioning (Figure, point a) and further supplementation provides no additional benefit (Figure, point b). Three RCTs examining the effect of vitamin E supplementation on cognition have been published and all have null results.4–6 Of note, none of these trials targeted individuals who had low dietary intake. Post hoc analyses reported in 2 of the trials suggested that this could have accounted for the absence of effect. In the Women’s Health Study, among women whose vitamin E consumption at baseline was less than the median intake of 6.1 mg per day, vitamin E treatment of 435 mg every other day significantly slowed the rate of cognitive decline compared with placebo (rate difference=0.05), whereas there was no effect among women whose baseline intake was greater than 6.1 mg per day (rate difference of −0.01; P value for interaction=.04).4 In a similar post hoc analysis for the Women’s Antioxidant and Cardiovascular Study (WACS), there was no significant effect of intake of 402 mg of vitamin E on alternate days among women whose baseline intake levels were less than the median of 15 mg per day, currently the recommended dietary allowance (RDA).5 This raises the question of whether 15 mg per day is already within the range of optimum cognitive health and thus too high for observing a protective effect with additional supplementation. To further complicate interpretation of these data, trial participants were allowed to take multivitamin supplements containing nutrient levels that were as high as RDA levels; thus reported baseline levels were likely higher during the course of the trial. The Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFCS) also tested effects on cognition of B-vitamin supplementation, including folic acid (2.5 mg/d), vitamin B12 (1 mg/d), and vitamin B6 (50 mg/d).7 Overall, there was no effect of B-vitamin supplementation on cognitive decline but protective effects were observed among women who had dietary folate intakes of less than 279 mg per day (mean difference of 1.24 in cognitive change scores for B-vitamin treatment vs placebo compared with −0.04 among women with intakes ≥279 mg/d; P value for interaction=.002); vitamin B12 intakes less than the RDA of 2.4 μg per day (mean difference of 1.35 vs 0.10 in individuals with intakes ≥2.4 μg/d; P value for interaction=.05); and low intakes of at least 1 of the B vitamins (mean difference of 0.74 vs −0.10 in individuals with adequate intakes, P value for interaction=.01). The Folic Acid Cognitive Intervention Trial (FACIT) is a rare example of a vitamin supplement trial that targeted individuals who were found to have insufficient folate nutriture based on a stringent set of biochemical criteria.8 Participants were randomized to receive 800 μg per day of folic acid or placebo for 3 years. During this period, folate levels among treated individuals increased from a median 12 nmol/L to 76 nmol/L and homocysteine concentrations decreased from a median 13.0 μmol/L to 10.1 μmol/L. The folic acid–treated participants had significantly slower rates of decline in cognitive function on multiple tests compared with the placebo group. Published and ongoing RCTs of the effect of docosahexaenoic acid, an omega-3 fatty acid in fish oil, on cognitive decline and dementia have the same design flaw. The published trials report null findings. The exclusion criteria for these trials at best omitted persons who consumed more than 3 fish meals per week.9,10 This is far above the level of just 1 fish meal per week observed to be inversely associated with dementia in the majority of prospective epidemiological studies. The epidemiological literature strongly supports exclusion of individuals from supplement trials who consume fish more than occasionally (eg, rarely or never). Clinical trials are both costly and important for substantiation of nutrient effects on health. The public health may be better served by initially conducting trials in individuals with insufficient nutriture and, if effective, further testing the effectiveness in those with adequate nutrient levels.

The homocysteine controversy

Abstract: Mild to moderate hyperhomocysteinemia has been identified as a strong predictor of cardiovascular disease, independent from classical atherothrombotic risk factors. In the last decade, a number of large intervention trials using B vitamins have been performed and have shown no benefit of homocysteine-lowering therapy in high-risk patients. In addition, Mendelian randomization studies failed to convincingly demonstrate that a genetic polymorphism commonly associated with higher homocysteine levels (methylenetetrahydrofolate reductase 677 C>T) is a risk factor for cardiovascular disease. Together, these findings have cast doubt on the role of homocysteine in cardiovascular disease pathogenesis, and the homocysteine hypothesis has turned into a homocysteine controversy. In this review, we attempt to find solutions to this controversy. First, we explain that the Mendelian randomization analyses have limitations that preclude final conclusions. Second, several characteristics of intervention trials limit interpretation and generalizability of their results. Finally, the possibility that homocysteine lowering is in itself beneficial but is offset by adverse side effects of B vitamins on atherosclerosis deserves serious attention. As we explain, such side effects may relate to direct adverse effects of the B-vitamin regimen (in particular, the use of high-dose folic acid) or to proinflammatory and proproliferative effects of B vitamins on advanced atherosclerotic lesions.

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

Abstract: Despite the targeting of traditional risk factors for cardiovascular disease, disease burden has not been completely eliminated. Thiamine is an essential cofactor in carbohydrate metabolism and individuals with diabetes are thiamine deficient. The pathophysiology of recognised complications of thiamine deficiency is similar to that underlying atherosclerosis and the metabolic syndrome, namely oxidative stress, inflammation and endothelial dysfunction. This review examines the mechanisms by which thiamine deficiency occurs in individuals with diabetes, how this deficiency leads to hyperglycaemic-induced damage, and the effect of thiamine replacement on vascular disease, endothelial function and oxidative stress. Thiamine administration can prevent the formation of harmful by-products of glucose metabolism, reduce oxidative stress and improve endothelial function. The potential benefit of long-term replacement in those with diabetes is not yet known but may reduce cardiovascular risk and angiopathic complications.

Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial.

Abstract: Background: Polycystic ovary syndrome is the most common cause of chronic anovulation infertility in women in fertile period, and it's characterized by an increased produc- tion of androgens and estrogens. The adminis- tration of D-chiro-inositol, a B complex vitamin, was associated with a decreased of serum testosterone and simultaneously, due to its abili- ty to increase insulin sensitivity, women who re- ceived D-chiro-inositol showed a great improve- ment of the ovulary function. Besides, the sup- plementation of inositol improves the oocytes' quality and increase the number of oocytes col- lected after ovarian stimulation in patients un- dergoing IVF (in vitro fertilization). Aim: The aim of this study is to determine the effects of myo-inositol on oocyte's quality on a sample of women with polycystic ovary syndrome. Material and Methods: The patients were di- vided into two groups: patients of Group A in- took 2 g of myo-inositol + 200 µg of folic acid (In- ofolic ® , LO.LI. Pharma, Rome, Italy) while Group B only 200 µg of folic acid, both groups took the treatment twice a day, continuously for 3 months. Results: At the end of treatment, the number of follicles of diameter >15 mm, visible at ultra- sound during stimulation, and the number of oocytes recovered at the time of pick-ups were found to be significantly greater in the group treated with myo-inositol, so as the aver-age number of embryos transferred and embryo Score S1. Significantly reduced was the average number of immature oocytes (vesicles germ and degenerated oocytes) too. Conclusions: These data suggest that myo- inositol may be useful in the treatment of PCOS patients undergoing ovulation induction, both for its insulin-sensitizing activity, and its role in oocyte maturation.

Alcohol-related peripheral neuropathy: nutritional, toxic, or both?

Abstract: Alcohol-related peripheral neuropathy (ALN) is a potentially debilitating complication of alcoholism that results in sensory, motor, and autonomic dysfunction. Unfortunately, ALN is rarely discussed as a specific disease entity in textbooks because it is widely assumed to primarily reflect consequences of nutritional deficiency. This hypothesis is largely based on observations first made over eight decades ago when it was demonstrated that thiamine deficiency (beriberi) neuropathy was clinically similar to ALN. In recent studies, failure of thiamine treatment to reverse ALN, together with new information demonstrating clinical and electrophysiological distinctions between ALN and nutritional deficiency neuropathies, suggests that alcohol itself may significantly predispose and enhance development of neuropathy in the appropriate clinical setting. We reviewed the evidence on both sides and conclude that ALN should be regarded as a toxic rather than nutritional neuropathy.

DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models

Abstract: Late-onset Alzheimer's disease seems to be a multi-factorial disease with both genetic and non-genetic, environmental, possible causes. Recently, epigenomics is achieving a major role in Alzheimer's research due to its involvement in different molecular pathways leading to neurodegeneration. Among the different epigenetic modifications, DNA methylation is one of the most relevant to the disease. We previously demonstrated that presenilin1 (PSEN1), a gene involved in amyloidogenesis, is modulated by DNA methylation in neuroblastoma cells and Alzheimer's mice in an experimental model of nutritionally altered one-carbon metabolism. This alteration, obtained by nutritional deficiency of B vitamins (folate, B12 and B6) hampered S-adenosylmethionine (SAM)-dependent methylation reactions. The aim of the present paper was to investigate the regulation of DNA methylation machinery in response to hypomethylating (B vitamin deficiency) and hypermethylating (SAM supplementation) alterations of the one-carbon metabolism. We found that DNA methylases (DNMT1, 3a and 3b) and a putative demethylase (MBD2) were differently modulated, in line with the previously observed changes of PSEN1 methylation pattern in the same experimental conditions.

Polypharmacy and nutritional status in older adults: a cross-sectional study.

Abstract: Background: Older adults have more chronic medical conditions, and the level of polypharmacy increases with advancing age. Malnutrition and drug nutrient interactions are of concern in this population. Objectives: The aims of this cross-sectional study were to examine nutritional status, the use of medications, and drug-nutrient interactions in older adults. Methods: Interviewer-administered surveys were conducted in 1100 community-dwelling older (age >65 years) adults. Information regarding demographics, nutritional status, medical history and medication usage was obtained. Self-reported data were verified by third parties when feasible. Informed consent and Human Subjects Committee approval were obtained. A pilot conducted prior to the onset of the study revealed high rates of inter-rater reliability. Data were recorded and entered into Excel spreadsheets for coding and cleaning and transferred to SPSS v. 17.0 for analyses. Results: The respondents’ mean age was 75.5 years. The top six most frequently used classes of medications were gastrointestinal agents, antihypertensives, diuretics, analgesics, β-adrenoceptor antagonists and antihyperlipidaemics. The prevalence of polypharmacy among the participants was 43.4%, with 51.1% of those participants using five or more medications. Most notable was the statistically significant inverse correlation between increasing number of medications and intake of fibre. Intake of cholesterol, glucose and sodium were positively associated with increasing medication use. A trend was also observed for increased phosphorus intake and increased number of medications used. Intake of fat-soluble vitamins, B vitamins, carotenoids and minerals was lower in those with increasing number of medications. Decrements in physical health were associated with decreasing intake of many fat-soluble and water-soluble vitamins, major minerals, trace minerals and electrolytes. Excessive macronutriture, specifically relating to the intake of saturated fats, refined carbohydrates and cholesterol, along with decreased intake of fibre and bioavailable protein sources, was also associated with poor physical health. Conclusions: The number of medications used by older adults in this convenience sample was associated with poorer nutritional status. Decrements in physical health have a statistically significant effect on nutrient intake. Further research into these issues is required.

Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme.

Abstract: Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immunodeficiencies in adults They comprise a heterogeneous group of pathologies, with frequent non-infectious complications in addition to the bacterial infections that usually characterize their presentation Complications include a high risk of malignancy, especially lymphoma and gastric cancer Helicobacter pylori infection and pernicious anaemia are risk predictors for gastric cancer in the general population and probably in patients with CVIDs Screening for gastric cancer in a high-risk population appears to improve survival Given the increased risk of gastric cancer in patients with CVIDs and prompted by a case of advanced gastric malignancy in a patient with a CVID and concomitant pernicious anaemia, we performed a review of the literature for gastric cancer and conducted a cohort study of gastric pathology in 116 patients with CVIDs under long-term follow-up in Oxford Regardless of the presence of pernicious anaemia or H pylori infection, patients with CVIDs have a 10-fold increased risk of gastric cancer and are therefore a high-risk population Although endoscopic screening of all patients with CVIDs could be considered, a more selective approach is appropriate and we propose a surveillance protocol that should reduce modifiable risk factors such as H pylori, in order to improve the management of patients with CVIDs at risk of gastric malignancy

Thiamine (Vitamin B1)

Abstract: Thiamine (vitamin B 1) was the first B vitamin to have been identified. It serves as a cofactor for several enzymes involved in energy metabolism. The thiamine-dependent enzymes are important for the biosynthesis of neurotransmitters and for the production of reducing substances used in oxidant stress defenses, as well as for the synthesis of pentoses used as nucleic acid precursors. Thiamine plays a central role in cerebral metabolism. Its deficiency results in dry beriberi, a peripheral neuropathy, wet beriberi, a cardiomyopathy with edema and lactic acidosis, and Wernicke—Korsakoff syndrome, whose manifestations consist of nystagmus, ophthalmoplegia, and ataxia evolving into confusion, retrograde amnesia, cognitive impairment, and confabulation. Patients on a strict thiamine-deficient diet display a state of severe depletion within 18 days. The most common cause of thiamine deficiency in affluent countries is either alcoholism or malnutrition in nonalcoholic patients. Treatment by thiamine supplementat...