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1.
What dose of folic acid to use with methotrexate in rheumatoid arthritis?
Bramley, D
Drug and therapeutics bulletin. 2021;(7):103-106
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Periconceptional Folate Supplementation in Women after Bariatric Surgery-A Narrative Review.
Vynckier, AK, Ceulemans, D, Vanheule, G, De Mulder, P, Van Den Driessche, M, Devlieger, R
Nutrients. 2021;(5)
Abstract
The prevalence of obesity is increasing globally, and along with it, there is a growing number of patients opting to undergo bariatric surgery to treat this condition. Whilst it has many advantages, bariatric surgery is known to induce micronutrient deficiency, with possible deleterious effects on overall health. This topic becomes even more relevant during pregnancy, where deficiencies can also affect the developing fetus, possibly being the cause of an increase in congenital anomalies. Most notably amongst these micronutrients is folate, or vitamin B9, which plays an essential role in development, gene expression and genomic stability. As insufficient levels of folate are associated with neural tube defects in the fetus, preventing and treating folate deficiencies during pregnancies after bariatric surgery is a relevant issue. Unfortunately, folate supplementation recommendations for bariatric patients who wish to become pregnant are not clear. In this narrative review, we discuss whether the recommendations for the general population are still valid for bariatric patients. Furthermore, we discuss the role of folate in the human body, folate status in both non-bariatric and bariatric patients, the various types of folate that are available for substitution and the risk associated with over-supplementation.
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3.
Effects of Supplementation with Folic Acid and Its Combinations with Other Nutrients on Cognitive Impairment and Alzheimer's Disease: A Narrative Review.
Puga, AM, Ruperto, M, Samaniego-Vaesken, ML, Montero-Bravo, A, Partearroyo, T, Varela-Moreiras, G
Nutrients. 2021;(9)
Abstract
Cognitive impairment and Alzheimer's Disease, among other cognitive dysfunctions, has been recognized as a major public health problem. Folic acid is a well-known essential nutrient whose deficiency has been linked to neurocognitive dysfunctions, owing to hyperhomocysteinemia, an independent risk factor for cardio- and cerebrovascular diseases, including cognitive impairment, Alzheimer's Disease, and vascular dementia. However, to date, there is certain controversy about the efficacy of vitamin supplementation in patients with these pathologies. Therefore, we have reviewed the available dietary intervention studies based on folic acid, either alone or in combination with different vitamins or nutrients into the progression of Alzheimer's Disease and Cognitive impairment, highlighting the cognition and biochemical markers employed for the evaluation of the disease progression. Undeniably, the compiled information supports the potential benefits of vitamin supplementation in these pathologies, especially relevant to the aging process and quality of life, although more research is urgently needed to confirm these positive findings.
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4.
Alterations in Sulfur Amino Acids as Biomarkers of Disease.
Stabler, SP
The Journal of nutrition. 2020;(Suppl 1):2532S-2537S
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Abstract
Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to tetrahydrofolate, which is required for DNA and RNA synthesis. Deficiency of either of the cobalamin (Cbl) and/or folate cofactors results in elevated Hcy and megaloblastic anemia. Elevated Hcy is a sensitive biomarker of Cbl and/or folate status and more specific than serum vitamin assays. Elevated Hcy normalizes when the correct vitamin is given. Elevated Hcy is associated with alcohol use disorder and drugs that target folate or Cbl metabolism, and is a risk factor for thrombotic vascular disease. Elevated methionine and cystathionine are associated with liver disease. Elevated Hcy, cystathionine, and cysteine, but not methionine, are common in patients with chronic renal failure. Higher cysteine predicts obesity and future weight gain. Serum S-adenosylhomocysteine (AdoHcy) is elevated in Cbl deficiency and chronic renal failure. Drugs that require methylation for catabolism may deplete liver S-adenosylmethionine and raise AdoHcy and Hcy. Deficiency of Cbl or folate or perturbations of their metabolism cause major changes in sulfur amino acids.
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One-carbon metabolism and folate transporter genes: Do they factor prominently in the genetic etiology of neural tube defects?
Steele, JW, Kim, SE, Finnell, RH
Biochimie. 2020;:27-32
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Abstract
Neural tube defects (NTDs) are a broad class of congenital birth defects that result from the failure of neural tube closure during neurulation. Folic acid supplementation has been shown to prevent the occurrence of NTDs by as much as 70% in some human populations, and folate deficiency in a pregnant woman is associated with increased risk for having an NTD affected infant. Thus, folate transport-related genes and genes involved in the subsequent folate-mediated one-carbon metabolic pathway have long been considered primary candidates to study the genetic etiology of human NTDs. Herein, we review the genes involved in folate transport and one-carbon metabolism thus far identified as contributing variants that influence human NTD risk, and place these findings in the context of our evolving understanding of the complex genetic architecture underlying these defects.
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Laboratory approach to investigation of anemia with a focus on pyruvate kinase deficiency.
Agarwal, AM, Rets, A
International journal of laboratory hematology. 2020;:107-112
Abstract
Anemia is a major health burden worldwide and affects approximately one-third of world's population. It is not a diagnosis; it is a manifestation of an underlying pathophysiology leading to either decreased hemoglobin (Hb), hematocrit (Hct), or red blood cells (RBCs). Iron deficiency anemia is still the most common cause of anemia worldwide. The symptoms are usually due to the underlying compensatory responses to decrease in oxygen delivery to the tissues. Laboratory investigation should start with complete blood count (CBC), reticulocyte count (RC), and peripheral smear evaluation. Further testing depends on these indices, that is, iron parameters and hemoglobinopathies/thalassemia evaluation in microcytic hypochromic anemia, vitamin B12, and folic acid level in macrocytic anemia. Increased RC denotes adequate bone marrow response and points toward hemolytic process and vice versa. Anemia diagnosis can be complex and confusing for the practicing physician. This review tries to give a practical simplistic approach to the diagnosis, focusing mainly on the basic parameters, that is, CBC, RC, and peripheral smear etc. Moreover, we have also tried to provide an update on the pyruvate kinase deficiency, as there has been recent exciting development in the management of these patients.
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Fallacies of clinical studies on folic acid hazards in subjects with a low vitamin B12 status.
van Gool, JD, Hirche, H, Lax, H, Schaepdrijver, L
Critical reviews in toxicology. 2020;(2):177-187
Abstract
A 2016 plea for revision of the 1 mg/day upper level of folic acid intake prompted us to comprehensively review the 1945-2017 literature on folic acid hazards in subjects with low cyanocobalamin. The concept of folic acid treatment 'masking' the anemia in undiagnosed cyanocobalamin deficiency, thereby delaying the diagnosis of neuropathy, does not account for the dissociation between the deficiency's hematologic and neurologic manifestations. Possible risks of this concept were addressed by 1963-1971 FDA rulings, classifying all folic acid preparations as prescription-only drugs, delivering ≤1 mg daily. The neuropathy in folic acid trials for 'pernicious anemia' is due to the singular use of folic acid-neuropathy improved or disappeared with replacement of folic acid by liver extract or cyanocobalamin. The hypothesis that cognitive impairment in 'subclinical' cyanocobalamin deficiency is folate-mediated is untenable. Of 6 papers specifically investigating this, none could prove that increased cognitive impairment was related to high folate intake. This review fully supports the safety of the 1 mg/day upper level for folic acid intake.
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Folate and macrophage folate receptor-β in idiopathic pulmonary fibrosis disease: the potential therapeutic target?
Qu, Y, Hao, C, Zhai, R, Yao, W
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020;:110711
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal disease with high mortality and poor prognosis. It is characterized by a gradual decline in lung function, and there are currently no effective therapeutic methods. Folate is a water-soluble B vitamin that plays an important role in one-carbon transfer reactions, nucleic acid biosynthesis and methylation reactions. Studies have shown that folate may participate in the pathogenesis of IPF through ways of DNA repair, methylation, and reactive oxygen species. Macrophage activation is an important early cellular event in IPF and the inflammatory response that they trigger is a significant feature of IPF. Folate receptor-β (FR-β) is a cell surface glycosylphosphatidylinositol-anchored glycoprotein that can mediate the unidirectional transport of folate into cells. And it has been found in previous studies that FR-β is usually overexpressed on activated macrophages, but the expression on resting macrophages was undetectable. Therefore, targeting FR-β may have potential value for the early diagnosis and therapy of IPF. Our goal is to highlight the biological role of folate and FR-β in IPF, and we hope to provide helpful insight for clinical treatment strategies.
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Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.
Cappuccilli, M, Bergamini, C, Giacomelli, FA, Cianciolo, G, Donati, G, Conte, D, Natali, T, La Manna, G, Capelli, I
Nutrients. 2020;(5)
Abstract
Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.
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Bacterial folate biosynthesis and colorectal cancer risk: more than just a gut feeling.
Kok, DE, Steegenga, WT, Smid, EJ, Zoetendal, EG, Ulrich, CM, Kampman, E
Critical reviews in food science and nutrition. 2020;(2):244-256
Abstract
Folate is a B-vitamin with an important role in health and disease. The optimal folate status with regard to human health remains controversial. A low intake of natural folate as well as excessive intake of synthetic folic acid, were previously linked to an increased risk of colorectal cancer or with aberrant molecular pathways related to carcinogenesis in some studies. Importantly, most studies conducted so far, solely focused on dietary intake or circulating levels of folate in relation to cancer risk. Notably, diet or dietary supplements are not the only sources of folate. Several bacteria in the gastrointestinal tract can synthesize B-vitamins, including folate, in quantities that resemble dietary intake. The impact of bacterial folate biosynthesis concerning human health and disease remains unexplored. This review highlights current insights into folate biosynthesis by intestinal bacteria and its implications for processes relevant to cancer development, such as epigenetic DNA modifications and DNA synthesis. Moreover, we will reflect on the emerging question whether food-grade or intestinal bacteria can be considered a potential target to ensure sufficient levels of folate in the gastrointestinal tract and, hence the relevance of bacterial folate biosynthesis for disease prevention or treatment.