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Molecules (Basel, Switzerland) May 2022Mitochondrial diseases (MDs) may result from mutations affecting nuclear or mitochondrial genes, encoding mitochondrial proteins, or non-protein-coding mitochondrial... (Review)
Review
Mitochondrial diseases (MDs) may result from mutations affecting nuclear or mitochondrial genes, encoding mitochondrial proteins, or non-protein-coding mitochondrial RNA. Despite the great variability of affected genes, in the most severe cases, a neuromuscular and neurodegenerative phenotype is observed, and no specific therapy exists for a complete recovery from the disease. The most used treatments are symptomatic and based on the administration of antioxidant cocktails combined with antiepileptic/antipsychotic drugs and supportive therapy for multiorgan involvement. Nevertheless, the real utility of antioxidant cocktail treatments for patients affected by MDs still needs to be scientifically demonstrated. Unfortunately, clinical trials for antioxidant therapies using α-tocopherol, ascorbate, glutathione, riboflavin, niacin, acetyl-carnitine and coenzyme Q have met a limited success. Indeed, it would be expected that the employed antioxidants can only be effective if they are able to target the specific mechanism, i.e., involving the central and peripheral nervous system, responsible for the clinical manifestations of the disease. Noteworthily, very often the phenotypes characterizing MD patients are associated with mutations in proteins whose function does not depend on specific cofactors. Conversely, the administration of the antioxidant cocktails might determine the suppression of endogenous oxidants resulting in deleterious effects on cell viability and/or toxicity for patients. In order to avoid toxicity effects and before administering the antioxidant therapy, it might be useful to ascertain the blood serum levels of antioxidants and cofactors to be administered in MD patients. It would be also worthwhile to check the localization of mutations affecting proteins whose function should depend (less or more directly) on the cofactors to be administered, for estimating the real need and predicting the success of the proposed cofactor/antioxidant-based therapy.
Topics: Anticonvulsants; Antioxidants; DNA, Mitochondrial; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Precision Medicine
PubMed: 35684429
DOI: 10.3390/molecules27113494 -
European Journal of Nutrition Oct 2022To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B status among young Laotian children. (Randomized Controlled Trial)
Randomized Controlled Trial
Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B status among young Laotian children: a randomized controlled trial.
PURPOSE
To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B status among young Laotian children.
METHODS
Children (n = 1704) aged 6-23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline.
RESULTS
There was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015).
CONCLUSIONS
Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B status in young Laotian children.
TRIAL REGISTRATION
The trial was registered at www.
CLINICALTRIALS
gov (NCT02428647) on April 29 2015.
Topics: Child; Dietary Supplements; Folic Acid; Humans; Laos; Micronutrients; Nutritional Status; Powders; Riboflavin; Thiamine; Vitamin B 12; Vitamins
PubMed: 35534778
DOI: 10.1007/s00394-022-02890-3 -
The Journal of International Advanced... Mar 2022The Brown-Vialetto-Van Laere syndrome or the riboflavin transporter deficiency syndrome is a neurodegenerative disorder initially reported by Brown in 1894, by Vialetto...
The Brown-Vialetto-Van Laere syndrome or the riboflavin transporter deficiency syndrome is a neurodegenerative disorder initially reported by Brown in 1894, by Vialetto in 1936, and by Van Laere in 1966. The syndrome has been described in more than 100 patients since then. Hearing loss is the most common symptom of the syndrome, as most individuals have it through the development of the disease. Although there is a variation between the onset of hearing loss and the other possible symptoms, hearing loss usually begins in early childhood. Nevertheless, there are some cases describing hearing loss starting in adults. Hereby, we present a case report of a patient who started having the symptoms at the age of 14 and who had a mutation in the SLC52A3 gene, presenting with sensorineural hearing loss associated with cerebellar ataxia, who also underwent successful cochlear implant surgery.
Topics: Adolescent; Bulbar Palsy, Progressive; Cochlear Implants; Deafness; Hearing Loss, Sensorineural; Humans; Membrane Transport Proteins
PubMed: 35418370
DOI: 10.5152/iao.2022.21159 -
Public Health Nutrition Apr 2022To validate a Food Diversity Questionnaire (CDA, for its name in Spanish) that identifies the prevalence of the risk of deficiency in the intake of eleven micronutrients.
OBJECTIVE
To validate a Food Diversity Questionnaire (CDA, for its name in Spanish) that identifies the prevalence of the risk of deficiency in the intake of eleven micronutrients.
DESIGN
The CDA paper form, an online application for data entry and handling, was designed and compared with the 24-h recall (24HR) as a reference method. All data were processed in Personal Computer Software for Intake Distribution Estimation (PC-SIDE) v1 software. A descriptive analysis and comparisons between prevalence, concordance and reproducibility analyses were performed.
SETTING
Medellín, Colombia.
PARTICIPANTS
Women of childbearing age between 19 and 50 years ( 186) who worked for the Buen Comienzo programme in 2019.
RESULTS
When comparing the adjusted 24HR technique and the CDA, there was no significant difference in population-level data at risk of deficiency in any micronutrient intake. However, based on individual-level data of the best linear unbiased predictor, the concordance analyses were weak, and although agreements were high according to the diagnostic performance tests, a good ability to detect deficiency was only observed in a few nutrients: vitamin A 100·0 %, Ca 98·7 %, Fe 92·8 %, folates 91·6 %, and pyridoxine 81·8 %.
CONCLUSIONS
The CDA validated in this study is useful and faster at evaluating population-level data at risk of deficiency in the intake of Ca, Fe, Zn, thiamine, riboflavin, niacin, pyridoxine, folates, vitamin B, vitamin C and vitamin A. Based on individual-level data, a good ability to detect deficiencies was observed in the intake of vitamin A, Ca, Fe, folates and pyridoxine.
PubMed: 35393003
DOI: 10.1017/S1368980022000854 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2022Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome.
OBJECTIVE
This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement".
METHODS
The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations.
RESULTS
There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed.
CONCLUSION
This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.
Topics: Dietary Supplements; Humans; Micronutrients; Trace Elements; Vitamin A; Vitamins
PubMed: 35365361
DOI: 10.1016/j.clnu.2022.02.015 -
Frontiers in Neurology 2022Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation due to deficiency of the mitochondrial electron transfer...
BACKGROUND
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation due to deficiency of the mitochondrial electron transfer chain. The late-onset form is characterized by exercise intolerance, muscle weakness, and lipid storage in myofibers. Most MADD patients greatly benefit from riboflavin supplementation.
PATIENTS AND METHODS
A retrospective study was conducted on patients with a diagnosis of vacuolar myopathy with lipid storage followed in our neuromuscular unit in the last 20 years. We selected 10 unrelated patients with the diagnosis of MADD according to clinical, morphological, and biochemical aspects. Clinical features, blood tests including serum acylcarnitines, EMG, and ENG were revised. Muscle biopsy was performed in all, and one individual underwent also a sural nerve biopsy. Gene sequencing of , and was performed as a first-tier genetic analysis followed by next-generation sequencing of an hyperCKemia gene panel in patients with undefined genotypes.
RESULTS
Clinical evaluation at onset in all our patients showed fatigue and muscle weakness; four patients showed difficulties in chewing, three patients complained of dysphagia, two patients had a dropped head, and a patient had an unexpected ataxia with numbness and dysesthesia. Laboratory blood tests revealed a variable increase in serum CK (266-6,500) and LDH levels (500-2,000). Plasma acylcarnitine profile evidenced increased levels of different chains intermediates. EMG was either normal or showed myogenic or neurogenic patterns. NCS demonstrated sensory neuropathy in two patients. Muscle biopsies showed a vacuolar myopathy with a variable increase in lipid content. Nerve biopsy evidenced an axonal degeneration with the loss of myelinated fibers. genetic analysis identifies 14 pathogenic variants. Patients were treated with high doses of riboflavin (400 mg/die). All of them showed a rapid muscle strength improvement and normalization of abnormal values in laboratory tests. Neuropathic symptoms did not improve.
CONCLUSION
Our data confirmed that clinical features in MADD patients are extremely variable in terms of disease onset and symptoms making diagnosis difficult. Laboratory investigations, such as serum acylcarnitine profile and muscle biopsy evaluation, may strongly address to a correct diagnosis. The favorable response to riboflavin supplementation strengthens the importance of an early diagnosis of these disorders among the spectrum of metabolic myopathies.
PubMed: 35309592
DOI: 10.3389/fneur.2022.815523 -
Microorganisms Feb 2022The health benefits of probiotics are beyond doubt. The positive effects of lactobacilli and bifidobacteria on the function of many body systems have been repeatedly...
The health benefits of probiotics are beyond doubt. The positive effects of lactobacilli and bifidobacteria on the function of many body systems have been repeatedly proven by various studies. To completely realize the potential of probiotic microorganisms, the strains should be tested by the greatest combination of characteristics that contribute to the wellness of the host. In this work, for the first time, a combined assessment of the probiotic properties and vitamin B-producing potential of various species and strains of bifidobacteria and lactobacilli was carried out. The presence of an additional advantage, such as vitamin-producing ability, can prevent vitamin deficiency both at the level of the consumption of fermented foods, when the enrichment will occur naturally on the spot, and during colonization by these intestinal strains, when synthesis will occur in vivo. To select potential probiotics, the stress tolerance ability of 16 lactic acid bacteria and bifidobacteria strains to low pH values, bile, and proteolytic enzymes, as well as their ability to autoaggregate, were studied under conditions of modeling the gastrointestinal tract in vitro. The ability of the strains to extracellularly accumulate water-soluble B vitamins was evaluated by capillary electrophoresis. Among the tested strains of bifidobacteria, VKPM AC-1662 is of interest; it was characterized by the greatest stress tolerance ability and the ability to autoaggregate, in addition to the extracellular synthesis of riboflavin and pyridoxine. Among lactic acid bacteria, VKPM B-8936 demonstrated the greatest tolerance to low pH, VKPM B-11007 to duodenal conditions, VKPM B-2213 to pepsin, and VKPM B-2214 to pancreatin. The highest percentage of autoaggregation was observed in VKPM B-2214, which also accumulated the largest amount of pantothenic acid, but it was sensitive to stress conditions. The obtained results could be used to create new products enriched with probiotics and B vitamins.
PubMed: 35208924
DOI: 10.3390/microorganisms10020470 -
Poultry Science Apr 2022
PubMed: 35164946
DOI: 10.1016/j.psj.2021.101559 -
Frontiers in Immunology 2021Hemophagocytic lymphocytosis (HLH) is a rare disease caused by inborn errors of immunity (IEI), secondary to infection, lymphoma or autoimmune disorders, but we often...
Hemophagocytic lymphocytosis (HLH) is a rare disease caused by inborn errors of immunity (IEI), secondary to infection, lymphoma or autoimmune disorders, but we often overlook the fact that HLH can be secondary to inborn errors of metabolism (IEM). Here, we describe a patient who was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. The diagnosis of glutaric aciduria type IIC, a IEM, was confirmed by whole exome sequencing. The patient was treated with coenzyme Q10 and riboflavin which effectively improved her liver function. During treatment, the patient developed severe anemia and thrombocytopenia. Persistent fever, splenomegaly, cytopenias, increased ferritin, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis in the bone marrow pointed to the diagnosis of HLH; however, the patient eventually died of gastrointestinal bleeding. After other potential causes were ruled out, the patient was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. When cytopenias occurs in IEM patients, HLH is a possible complication that cannot be ignored. This case suggests a possible relationship between IEM and risk for immune dysregulation.
Topics: Adult; Biomarkers; Disease Susceptibility; Electron-Transferring Flavoproteins; Erythrocyte Indices; Female; Genetic Predisposition to Disease; Humans; Iron-Sulfur Proteins; Lymphohistiocytosis, Hemophagocytic; Magnetic Resonance Imaging; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Oxidoreductases Acting on CH-NH Group Donors; Phenotype; Tomography, X-Ray Computed
PubMed: 35095902
DOI: 10.3389/fimmu.2021.810677 -
Animal : An International Journal of... Jan 2022Data from breeder hens and chicks are particularly critical for the development of vitamin B2 recommendations for organic poultry. To test safe thresholds of...
Data from breeder hens and chicks are particularly critical for the development of vitamin B2 recommendations for organic poultry. To test safe thresholds of supplementation, 100 breeder hens (Hubbard JA 57 K) and ten cockerels were allocated to ten housing groups, with each receiving supplementation of either 4.0 (treatment CON) or 2.5 mg (treatment RED) riboflavin per kg feed. After 15 weeks of experimental feeding, 256 eggs were incubated. From the hatched chicks (Hubbard S757), 192 were allocated to four treatments based on their parents' treatment (CON- or RED-) and on their own supplementation of either 4.0 (-CON) or 2.5 mg (-RED) riboflavin per kg feed. Two groups of each combination (CON-CON, CON-RED, RED-CON, RED-RED), each with 24 chicks of both sexes, were fattened for nine weeks and slaughtered. Analysis of total riboflavin (sum of native concentrations and supplements) in the parent's feeds revealed an average, over the 15 weeks, of 7.8 and 5.8 mg per kg feed for CON and RED, respectively. Body weight, plumage integrity, gait appearance, footpad, claw and keel bone integrity, lesion scores, laying performance, and egg mass were found to be of similarly high levels for all hens without any treatment effects. Performance traits of the hens in both treatments reached the specifications of the producer for this genotype. Yolk and albumen riboflavin concentrations were not affected although yolk colour in the RED treatment group became darker. Fertility was not affected, and hatchability was 100 per cent. Total riboflavin concentrations in the broiler diets were on average, over 9 weeks, 8.2 and 6.1 mg/kg for CON and RED, respectively. In chicks, RED treatment of their parents led to significant depressions of feed intake and growth. The RED treatment of the chicks themselves also impaired growth. Growth rates of the CON-CON treatment were in line with the specifications of the producer for this genotype. Plumage scores, footpad integrity and walking appearance of the broilers, and dressing percentage of the carcasses were not affected by treatment. The RED treatment of chicks caused lower spleen and heart weights, while pancreas and liver weights, and liver riboflavin concentrations were not affected. In conclusion, supplementation of 4.0 mg/kg to organic diets did not evoke any health or performance problems for breeder hens or broiler chicks, while a supplementation level of 2.5 mg per kg feed led to reduced weight gains, although without any other riboflavin deficiency symptoms.
Topics: Animal Feed; Animals; Chickens; Diet; Dietary Supplements; Female; Fertility; Male; Riboflavin
PubMed: 34999564
DOI: 10.1016/j.animal.2021.100433