ABSTRACT
BACKGROUND: DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear. OBJECTIVES: The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation. METHODS: A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation. RESULTS: Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as "high risk" or "some concerns." Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo. CONCLUSION: Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.
Subject(s)
DNA Methylation , Vitamin B Complex , Humans , Animals , Folic Acid , Dietary Supplements , MicronutrientsSubject(s)
Ambulances , Emergency Medical Services/organization & administration , Violence , Communication , Computers , Humans , IsraelSubject(s)
Emergencies , First Aid , Mobile Health Units , Allied Health Personnel , Education, Medical , House Calls , Medicine , Physicians , Specialization , United StatesABSTRACT
A case is reported in which a previously healthy individual, having received an inadequate course of chicken soup in treatment of mild pneumococcal pneumonia, experienced a severe relapse, refractory to all medical treatment and eventually requiring thoracotomy. The pharmacology of chicken soup is reviewed and the dangers of abrupt termination of therapy are stressed.
Subject(s)
Pneumonia/therapy , Research , Wit and Humor as Topic , Clinical Trials as Topic , Humans , Male , Middle AgedSubject(s)
Darier Disease/complications , Kaposi Varicelliform Eruption/complications , Pregnancy Complications, Infectious , Adult , Female , Humans , Immunization, Passive , Kaposi Varicelliform Eruption/therapy , Pregnancy , Pregnancy Complications, Infectious/therapy , gamma-Globulins/therapeutic useSubject(s)
Antibodies , Friend murine leukemia virus/pathogenicity , Leukemia, Experimental/immunology , Polysaccharides/pharmacology , Animals , Antibody Formation , Antiviral Agents/pharmacology , Carbon Isotopes , Chromium Isotopes , Cytotoxicity Tests, Immunologic , Female , Hemagglutination Tests , In Vitro Techniques , Iodine Isotopes , Mice , Mice, Inbred Strains , Neutralization Tests , Spleen/cytology , Spleen/immunology , Splenomegaly/immunologySubject(s)
Friend murine leukemia virus , Leukemia, Experimental/immunology , Lymph Nodes/immunology , Plasma Cells , Polysaccharides/therapeutic use , Spleen/immunology , Animals , Female , Interferons/biosynthesis , Leukemia, Experimental/blood , Leukemia, Experimental/microbiology , Leukemia, Experimental/pathology , Lymph Nodes/microbiology , Lymph Nodes/pathology , Mice , Polysaccharides/administration & dosage , Spleen/microbiology , Spleen/pathologyABSTRACT
A single inoculation of statolon into mice with established Friend virus (FV) leukemia can suppress the viral infection and produce a clinical remission lasting many months. Eventually, however, most of the mice develop characteristic FV leukemia. Persistence of FV activity in the spleens of mice during clinical remission can be demonstrated by cell transfer and histopathologic studies. Transfer to normal mice of a large number of spleen cells (10(7)) from mice in remission produces FV leukemia, and transfer of a small number of cells (10(2)) produces immunity to FV challenge. Histopathologic examination reveals clusters of abnormal FV leukemia-like cells directly beneath the capsules of the spleens of mice in clinical remission.