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1.
Medicines associated with folate-homocysteine-methionine pathway disruption.
Vidmar, M, Grželj, J, Mlinarič-Raščan, I, Geršak, K, Dolenc, MS
Archives of toxicology. 2019;(2):227-251
Abstract
Folate is vital for cell development and growth. It is involved in one-carbon transfer reactions essential for the synthesis of purines and pyrimidines. It also acts in conjunction with cobalamin (vitamin B12) as a fundamental cofactor in the remethylation cycle that converts homocysteine to methionine. A deficiency in folate or vitamin B12 can lead to elevated homocysteine level, which has been identified as an independent risk factor in several health-related conditions. Adequate folate levels are essential in women of childbearing age and in pregnant women, and folate deficiency is associated with several congenital malformations. Low folate levels can be caused by dietary deficiencies, a genetic predisposition or treatment with medicines that affect folate concentration. Women who are pregnant or of child-bearing age commonly use medicines, so it is important to identify the basic biochemical mechanisms by which medicines interfere with the folate-homocysteine-methionine pathway. This review focuses on prescription medicines associated with folate disruption. It also summarizes their undesirable/toxic effects. Recommendations regarding folate supplementation during medical therapy are also reviewed.
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2.
Homocysteine: A modifiable culprit of cognitive impairment for us to conquer?
Ji, Y, Lyu, P, Jin, W, Li, X, Li, X, Dong, Y
Journal of the neurological sciences. 2019;:128-136
Abstract
BACKGROUND Cognitive impairment, including mild cognitive impairment and its progressive deterioration to dementia, results in great hazards to the patient and the surrounding society. While some of the risk factors are unmodifiable, such as age, lower educational attainment, and genetic factors, another proposed one-homocysteine, an amino acid produced in the methylation cycle of protein metabolism is modifiable by cheap and easily accessible B-vitamins treatments in medical practice. OBJECTIVE AND METHODS To investigate the relationship between homocysteine and cognitive impairment, elucidate the underlying pathophysiological mechanisms and exploit any potential therapeutic values of homocysteine-lowering treatments in prevention and/or treatment in cognitive decline, we searched on the PUBMED databases surrounding around the physiological homocysteine metabolism, detrimental effects of abnormal homocysteine concentrations on the brain, and review observational and interventional experiments to date estimating the relationship between homocysteine and cognitive impairment with relatively powerful evidence. RESULTS Intrinsic and environmental factors help maintain the normal homocysteine concentrations, and pathological homocysteine concentrations exert adverse effects mediated by cellular and vascular pathways. Although many observational studies have suggested a causal link between hyperhomocysteinemia and cognitive impairment, the majority of randomized controlled trials failed to observe marked benefits on cognition by homocysteine-lowering treatments using B-vitamins, partly arising from some design limitations including: not identifying individuals at earlier stages of cognitive impairment who are most likely to benefit, overlooking any latent safety hazards of multiple vitamin supplementation, lack of sensitive and domain-specific cognitive tests, and interference of other underappreciated factors. CONCLUSION More studies are required to better explain the related pathophysiological mechanisms, improve experimental methods, and investigate the preventive or/and therapeutic effects of homocysteine-lowering strategies on cognitive impairment.
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3.
Nutritional Deficiencies, Bariatric Surgery, and Serum Homocysteine Level: Review of Current Literature.
Komorniak, N, Szczuko, M, Kowalewski, B, Stachowska, E
Obesity surgery. 2019;(11):3735-3742
Abstract
Obesity is currently one of the biggest global health problems. In the case of severe obesity, bariatric surgeries are considered to be the most important method of treatment. The 2 most commonly performed bariatric surgery procedures include Roux-en-Y gastric bypass and sleeve gastrectomy. However, these methods are not free from complications, and the most common ones (moderately long or long term) are micronutrient deficiencies. The deficiency of vitamins B6, B12, and folic acid as cofactors of the folate cycle contributes to the development of hyperhomocysteinemia. It seems that apart from nutritional factors, there are other aspects that have a significant influence on the concentration of homocysteine in blood, such as the type of conducted bariatric surgery, the post-surgical concentration of betaine and creatinine, and the clearance of methionine (i.e., the mutations of the gene that encodes the MTHFR reductase as well as other genes associated with the process of methylation, e.g., methionine synthase). Their presence might be one of the causes of the increased concentration of homocysteine after surgery despite the fact that patients take vitamin-mineral supplementation.
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4.
The Effects of Homocysteine on the Skeleton.
Saito, M, Marumo, K
Current osteoporosis reports. 2018;(5):554-560
Abstract
PURPOSE OF REVIEW Homocystinuria is a congenital metabolic disorder in which cystathionine β-synthase deficiency results in a prominent increase in homocysteine (serum levels > 100 μM), causing mental retardation, atherosclerotic cerebral infarction, and osteoporosis accompanied by fragility fractures. Encountering a case with excessive homocysteinemia such as that seen in hereditary homocystinuria is unlikely during usual medical examinations. However, in individuals who have vitamin B or folate deficiency, serum homocysteine concentrations are known to increase. These individuals may also have a polymorphism in methylenetetrahydrofolate reductase, MTHFR (C677T: TT type), which regulates homocysteine metabolism. These changes in homocysteine levels may elicit symptoms resembling those of homocystinuria (e.g., Alzheimer's disease, atherosclerosis, osteoporosis). RECENT FINDINGS High serum homocysteine has been shown to have detrimental effects on neural cells, vascular endothelial cells, osteoblasts, and osteoclasts. Homocysteine is also known to increase oxidative stress, disrupt cross-linking of collagen molecules, and increase levels of advanced glycation end products, which results in reduced bone strength through a mechanism that goes beyond low bone density and increased bone resorption. Therefore, high serum homocysteine may be regarded as a factor that can reduce both bone mass and impair bone quality. In this review, we outline the epidemiology and pathophysiology of osteoporosis associated with hyperhomocysteinemia.
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5.
The current status of homocysteine as a risk factor for cardiovascular disease: a mini review.
Chrysant, SG, Chrysant, GS
Expert review of cardiovascular therapy. 2018;(8):559-565
Abstract
Hyperhomocysteinemia has been considered as a risk factor for systemic atherosclerosis, cardiovascular disease (CVD) and stroke and many epidemiologic and case-controlled studies have demonstrated its association with these complications. In addition, treatment of hyperhomocysteinemia with folic acid ± B vitamins prevents the development of atherosclerosis, CVD and strokes. However, subsequent prospective, randomized, placebo-controlled trials have not shown an association of high homocysteine levels or their lowering with treatment with the incidence of atherosclerosis, CVD or strokes, due possibly, to the fortification of flower with folic acid. Therefore, at present, there is a controversy regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. Areas covered: For these reasons, a focused Medline search of the English language literature was conducted between 2010 and 2017 using the terms, homocysteine, risk factor, atherosclerosis, cardiovascular disease, stroke, treatment, and 38 papers with pertinent information were selected. Expert commentary: The review of data disclosed that there is a great controversy regarding the significance of homocysteine as a risk factor for CVD and stroke. The data from these papers together with collateral literature will be discussed in this mini review.
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6.
Colorectal polyp risk is linked to an elevated level of homocysteine.
Sun, M, Sun, M, Zhang, L, Shi, S
Bioscience reports. 2018;(2)
Abstract
Several studies have reported an association between levels of folate, homocysteine, and vitamin B12 and the risk of colorectal polyps. Here, our aim is to examine the possible effect of folate, homocysteine, and vitamin B12 levels on the risk of colorectal polyps by means of meta-analysis based quantitative synthesis. According to our inclusion/exclusion criteria, a total of 13 case-control studies were enrolled. The P-value of the association test, standard mean difference (SMD), and 95% confidence interval (CI) were calculated. Pooled analysis data showed a negative correlation between the risk of colorectal polyps and the levels of serum folate, red blood cell (RBC) folate, or vitamin B12 (all P>0.05). Nevertheless, for homocysteine level, we also observed a statistically significant difference between cases and controls in the overall and subgroup analysis of hospital-based control (HB), population-based control (PB), Chinese, Caucasian, or Asian (all P<0.05, SMD > 0). We found that increased levels of homocysteine may be statistically and significantly related to the risk of colorectal polyps.
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7.
Implication of homocysteine in diabetes and impact of folate and vitamin B12 in diabetic population.
Mursleen, MT, Riaz, S
Diabetes & metabolic syndrome. 2017;:S141-S146
Abstract
Diabetes mellitus is an acutely debilitating ailment affecting a large population of the world. At present, over 415 million people around the world including 7 million people in Pakistan suffering from diabetes. Homocysteine is an amino acid that is inversely related to vitamin B12 and folate, and raised level of homocysteine is implicated in many adverse health conditions. In this study, the potential role of homocysteine in diabetes and the epidemiology of hyperhomocysteinaemia, and vitamin B12 and folate deficiency is reviewed along with the impact of folate and vitamin B12 in regulation of homocysteine level. Deficiency of vitamin B12 and folate is rare in developed countries and the countries which adopted fortification programs, but deficiency of these vitamins is found to be highly prevalent in developing world, particularly in Pakistan. Several studies have found an association of high homocysteine levels and diabetes, but a few studies found contrary results. Hence, further epidemiological studies are recommended for homocysteine involvement in diabetes and vitamin B12 and folate deficiency, so that an urgent action can be taken to control the hyperhomocysteinaemia and consequently the ever increasing burden of disease and specifically diabetes.
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8.
Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta-analysis.
Dardiotis, E, Arseniou, S, Sokratous, M, Tsouris, Z, Siokas, V, Mentis, AA, Michalopoulou, A, Andravizou, A, Dastamani, M, Paterakis, K, et al
Multiple sclerosis and related disorders. 2017;:190-197
Abstract
BACKGROUND Multiple sclerosis (MS) is a demyelinating and disabling inflammatory disease of the central nervous system. Several factors contribute to MS pathogenesis including genetic-environmental interactions. Case-control studies suggest that there might be associations between MS and homocysteine (Hcy), vitamin B12, and folate blood levels. AIM: To meta-analyze all available data describing associations between MS and serum or plasma Hcy, vitamin B12, and folate levels. METHODS The PubMed, MEDLINE, and EMBASE databases were searched for eligible case-control studies published until June 2017. After data extraction, separate analyses using mainly random-effects models were conducted to test for associations between MS and vitamin B12, Hcy, or folate blood levels. RESULTS Twelve, 12, and 9 studies met the inclusion criteria for meta-analysis of MS and Hcy, vitamin B12, and folate levels, respectively. The standardized mean difference (SMD) between MS patients and controls was statistically significant for Hcy (SMD: 0.70, 95% CI: 0.06, 1.34). Stratification according to clinical pattern did not reveal significant differences between relapsing-remitting MS patients and controls (SMD: 0.30, 95% CI: -0.93, 1.54) or between secondary progressive MS patients and controls (SMD: 0.12, 95% CI: -1.65, 1.90). There were no significant differences in SMD between MS patients and healthy individuals for vitamin B12 (SMD: -0.09, 95% CI: -0.29, 0.10) or folate (SMD: -0.06, 95% CI: -0.17, 0.05). CONCLUSION MS patients tend to have elevated Hcy blood levels compared to healthy controls. Hcy may contribute to the pathogenesis of the disease.
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9.
Homocysteine: A Potential Common Route for Cardiovascular Risk and DNA Methylation in Psoriasis.
Wang, WM, Jin, HZ
Chinese medical journal. 2017;(16):1980-1986
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Abstract
OBJECTIVE Homocysteine is a sulfur-containing amino acid with potential clinical significance. Abnormal homocysteine levels have been found in patients with psoriasis. This review summarizes the possible correlations among homocysteine, cardiovascular risk, and DNA methylation in psoriasis. DATA SOURCES We retrieved the articles published in English from the PubMed database up to January 2017, using the keywords including "psoriasis," "homocysteine," "cardiovascular risk," "DNA methylation," "methylenetetrahydrofolate reductase," "MTHFR," and "MTHFR C677T." STUDY SELECTION Articles about the roles of homocysteine in the cardiovascular risk and DNA methylation in psoriasis were obtained and reviewed. RESULTS Observational studies consistently reported that elevated homocysteine is an independent risk factor for cardiovascular diseases. Several studies also consistently reported an association between psoriasis and increased cardiovascular risk. A substantial body of evidence also suggested that an elevated homocysteine level is related to the demethylation of DNA. Data from clinical trials also demonstrated that MTHFR C677T polymorphisms as well as DNA methylation aberrations are associated with psoriasis. CONCLUSIONS This review highlighted the relationships among homocysteine, cardiovascular risk, and DNA methylation, suggesting that homocysteine may be a biological link between cardiovascular risk and DNA methylation in psoriasis.
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10.
Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology.
Aboobakar, IF, Johnson, WM, Stamer, WD, Hauser, MA, Allingham, RR
Experimental eye research. 2017;:88-103
Abstract
Exfoliation syndrome (XFS) is a common age-related disorder that leads to deposition of extracellular fibrillar material throughout the body. The most recognized disease manifestation is exfoliation glaucoma (XFG), which is a common cause of blindness worldwide. Recent developments in XFS genetics, cell biology and epidemiology have greatly improved our understanding of the etiology of this complex inherited disease. This review summarizes current knowledge of XFS pathogenesis, identifies gaps in knowledge, and discusses areas for future research.