A.E. Perrin

Bio: A.E. Perrin is an academic researcher from University of Strasbourg. The author has contributed to research in topics: Vitamin B12 & Malabsorption. The author has an hindex of 6, co-authored 17 publications receiving 676 citations.

Vitamin B12 (cobalamin) deficiency in elderly patients

Abstract: VITAMIN B12 OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%–20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.

Anémies par carence en vitamine B12 chez le sujet âgé de plus de 75 ans : nouveaux concepts. À propos de 20 observations

Abstract: Resume Propos. – De nouveaux concepts ont ete recemment developpes sur les carences en vitamine B12 : l’existence chez la personne âgee d’un mecanisme frequent de non-dissociation de la vitamine B12 de sa proteine porteuse et la possibilite d’une supplementation par vitamine B12 cristalline per os. L’objectif de ce travail est de confirmer ces concepts sur une serie de patients âges de plus de 75 ans et presentant une anemie par carence en vitamine B12. Methodes. – Il s’agit d’une etude retrospective sur cinq ans. Elle inclut les patients âges de plus de 75 ans presentant une anemie (hemoglobine inferieure a 12 g/dL) par carence en vitamine B12 (B12 inferieure a 160 pg/mL). Resultats. – Vingt observations ont ete analysees. L’âge moyen des patients est de 82,5 ± 6 ans et le sex-ratio F/H est de 1,2. L’hemoglobine moyenne est a 7,9 ± 2,4 g/dL, la vitamine B12 serique a 83 ± 24 pg/mL et l’homocysteinemie a 35 ± 27 μmol/L. Les diagnostics retenus sont ceux de non-dissociation de la vitamine B12 (n = 10), de maladie de Biermer (n = 5), de malabsorption sur insuffisance pancreatique (n = 1) et de carence d’apports (n = 1). Parmi les non-dissociations de la vitamine B12, celles-ci sont liees a une gastrite atrophique et a la presence de Helicobacter pylori (n = 6), a la prise d’antiacides ou de biguanides (n = 3), a une exogenose (n = 2), ou sont idiopathiques (n = 2). Pour les patients avec un suivi (n = 10), l’administration de vitamine B12 par voie intramusculaire (n = 5) ou cristalline per os (n = 5) a permis la correction des anomalies de l’hemogramme. Conclusion. – Chez le sujet âge, la non-dissociation de la vitamine B12 est le principal mecanisme des carences en vitamine B12. Il est souvent lie a une gastrite atrophique. Le traitement par vitamine B12 cristalline per os est efficace et pourrait etre propose.

Carences en vitamine B12 avec test de Schilling normal ou syndrome de non-dissociation de la vitamine B12 de ses protéines porteuses chez le sujet âgé. Etude de 60 patients

Abstract: Resume Propos. – Plus de 15 % des personnes âgees de plus de 60 ans ont une carence en vitamine B12 (B12) en rapport avec un syndrome de non-dissociation de la B12 de ses proteines porteuses (ND B12). Mais jusqu'ici, seuls des cas cliniques isoles ou de petites series ont ete rapportees. Le but de cette etude etait de decrire les caracteristiques cliniques du syndrome de ND B12 chez des sujets âges. Methodes. – Soixante patients, âges de plus de 65 ans, presentant une carence en B12 par ND B12, ont ete extraits de la cohorte strasbourgeoise des carences en B12 (n = 169). Tous ces patients avaient un diagnostic de carence en B12 par ND B12 etabli et repondaient aux criteres du syndrome de ND B12 d'apres Carmel. Leurs donnees cliniques ont ete analysees retrospectivement. Resultats. – L'âge median des 60 patients etait de 75 ans et le rapport femme/homme etait de 2,3. Les symptomes cliniques principaux incluaient : polynevrite des membres inferieurs (35 %), confusion et demence (30 %) et manifestations en rapport avec la gravite de l'anemie telles qu'asthenie et œdemes des jambes (20 %). L'hemoglobine moyenne etait a 10,7 ± 2,5 g/dl et le volume globulaire moyen a 95,5 ± 13,8 fl. Il existait une anemie, une leucopenie, une thrombopenie et une pancytopenie dans respectivement 27 %, 18 %, 15 % et 5 % des cas. La B12 moyenne et l'homocysteinemie etaient a 138 ± 42 pg/ml et 22,5 ± 15,2 μmol/l. Aucun patient n'avait d'anticorps antifacteur intrinseque et le test de Schilling etait normal chez tous les patients. Les principaux desordres associes a la ND B12 etaient une gastrite atrophique (59%), la prise de metformine ou d'anti-acides (17 %), un ethylisme chronique (8 %) et une ND B12 idiopathique (n = 10). Un traitement par cyanocobalamine orale (500 ± 280 μg/j) a ete efficace chez 16 patients. Conclusions. – Cette etude montre que la carence en B12 par ND B12 s'accompagne chez le sujet âge de manifestations neurologiques et hematologiques severes dans environ 20 % des cas et que les desordres a l'origine de cette ND B12 sont multiples, notamment chez le sujet âge, avec en premier lieu la gastrite atrophique. Par ailleurs, elle illustre l'efficacite potentielle d'un traitement par B12 per os.

Sympathovagal response to orthostatism in overt and in subclinical hyperthyroidism.

Abstract: Heart rate variability (HRV) is a measure of the physiological variation of R-R intervals, reflecting the sympathovagal balance. In both overt and subclinical hyperthyroidism, a relative increase in sympathetic activity has been demonstrated, mainly due to a decrease in vagal activity. The modifications of HRV during orthostatism in normal subjects resemble those seen in hyperthyroidism. We have studied the response of 19 patients with overt hyperthyroidism and 12 with subclinical hyperthyroidism during orthostatism using HRV and compared the results to those of 32 healthy controls. In the three groups, the R-R intervals decreased in the same proportion after orthostatism. The low frequency power (LF)/[LF + high frequency power (HF)] ratio, which reflects the sympathetic tone, also increased in the same proportion in the three groups. However, the mechanisms of the modulation of the sympathovagal balance during orthostatism were different among the three groups. In controls, the relative increase of sympathetic tone after orthostatism was due principally to a decrease in vagal tone (reflected by decreased power in the HF band), while in overt hyperthyroidism, where the power in the HF band was already minimal in the lying position, there was a clear increase in the LF band power during orthostatism. The results were intermediate in the subclinical hyperthyroidism group, reflecting a continuum of effects of the thyroid hormone excess on the autonomic nervous system. Our study shows that despite an apparent normal cardiovascular adaptation to orthostatism in hyperthyroidism, the modulation of the autonomic nervous system is profoundly modified.

The human gut microbiome - A potential controller of wellness and disease

Abstract: Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

Vitamin B12 (cobalamin) deficiency in elderly patients

Abstract: VITAMIN B12 OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%–20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.

Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes.

Abstract: The human gut microbiota supplies its host with essential nutrients, including B-vitamins. Using the PubSEED platform, we systematically assessed the genomes of 256 common human gut bacteria for the presence of biosynthesis pathways for eight B-vitamins: biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin. On the basis of the presence and absence of genome annotations, we predicted that each of the eight vitamins was produced by 40-65% of the 256 human gut microbes. The distribution of synthesis pathways was diverse; some genomes had all eight biosynthesis pathways, whereas others contained no de novo synthesis pathways. We compared our predictions to experimental data from 16 organisms and found 88% of our predictions to be in agreement with published data. In addition, we identified several pairs of organisms whose vitamin synthesis pathway pattern complemented those of other organisms. This analysis suggests that human gut bacteria actively exchange B-vitamins among each other, thereby enabling the survival of organisms that do not synthesize any of these essential cofactors. This result indicates the co-evolution of the gut microbes in the human gut environment. Our work presents the first comprehensive assessment of the B-vitamin synthesis capabilities of the human gut microbiota. We propose that in addition to diet, the gut microbiota is an important source of B-vitamins, and that changes in the gut microbiota composition can severely affect our dietary B-vitamin requirements.

Homocysteine‐lowering interventions for preventing cardiovascular events

Abstract: Background Cardiovascular disease, which includes coronary artery disease, stroke and peripheral vascular disease, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor for cardiovascular disease is an elevated circulating total homocysteine level. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events has been investigated. This is an update of a review previously published in 2009, 2013, and 2015. Objectives To determine whether homocysteine-lowering interventions, provided to patients with and without pre-existing cardiovascular disease are effective in preventing cardiovascular events, as well as reducing all-cause mortality, and to evaluate their safety. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 5), MEDLINE (1946 to 1 June 2017), Embase (1980 to 2017 week 22) and LILACS (1986 to 1 June 2017). We also searched Web of Science (1970 to 1 June 2017). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. Selection criteria We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. Data collection and analysis We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We calculated the number needed to treat for an additional beneficial outcome (NNTB). We measured statistical heterogeneity using the I2 statistic. We used a random-effects model. We conducted trial sequential analyses, Bayes factor, and fragility indices where appropriate. Main results In this third update, we identified three new randomised controlled trials, for a total of 15 randomised controlled trials involving 71,422 participants. Nine trials (60%) had low risk of bias, length of follow-up ranged from one to 7.3 years. Compared with placebo, there were no differences in effects of homocysteine-lowering interventions on myocardial infarction (homocysteine-lowering = 7.1% versus placebo = 6.0%; RR 1.02, 95% confidence interval (CI) 0.95 to 1.10, I2 = 0%, 12 trials; N = 46,699; Bayes factor 1.04, high-quality evidence), death from any cause (homocysteine-lowering = 11.7% versus placebo = 12.3%, RR 1.01, 95% CI 0.96 to 1.06, I2 = 0%, 11 trials, N = 44,817; Bayes factor = 1.05, high-quality evidence), or serious adverse events (homocysteine-lowering = 8.3% versus comparator = 8.5%, RR 1.07, 95% CI 1.00 to 1.14, I2 = 0%, eight trials, N = 35,788; high-quality evidence). Compared with placebo, homocysteine-lowering interventions were associated with reduced stroke outcome (homocysteine-lowering = 4.3% versus comparator = 5.1%, RR 0.90, 95% CI 0.82 to 0.99, I2 = 8%, 10 trials, N = 44,224; high-quality evidence). Compared with low doses, there were uncertain effects of high doses of homocysteine-lowering interventions on stroke (high = 10.8% versus low = 11.2%, RR 0.90, 95% CI 0.66 to 1.22, I2 = 72%, two trials, N = 3929; very low-quality evidence). We found no evidence of publication bias. Authors' conclusions In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo. There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial. Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.