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Hyperhomocysteinemia and the role of B vitamins in cancer
Nadja Plazar, Mihaela Jurdana
Radiology and Oncology , 2010, DOI: 10.2478/v10019-010-0022-z
Abstract: Background. Patients suffering from malignancies have increased complications due to corresponding cardiovascular diseases and risk factor for the development of venous thromboembolism. Epidemiological studies have shown that increased homocysteine plasma concentration (hyperhomocysteinemia) is related to a higher risk of coronary heart disease, stroke, peripheral vascular disease and malignancies. Homocysteine (tHcy) is an intermediate sulfurcontaining amino acid produced from methionine during processing of dietary proteins. The plasma homocysteine levels are strongly influenced by diet, as well as by genetic factors. Folic acid, vitamins B6 and B12 are dietary components which influence the plasma homocysteine levels the most. Several studies have found that high blood levels of B vitamins are related to the integrity and function of DNA, and, are at least related to lower concentration of homocysteine. Folate depletion has been found to change DNA methylation and DNA synthesis in both animal and human studies. Because of this critical role of folate, most studies including homocysteine have focused on these two actions. Conclusions. Hyperhomocysteinemia proves to be the most common condition highly associated with both venous and arterial thrombosis in many cancer patients, while the associated pathophysiology has not been precisely established yet. Therefore, of current interest is the possible role of folate metabolism developing into a cancer initiating hyperhomocysteinemia. This review will discuss this possibility.
Folic Acid and Vitamins B12 Levels and Their Correlation in Cigarette Smoker with Hyperhomocysteinemia
Shahid A. Mujawar* and Vinayak W. Patil
Al Ameen Journal of Medical Sciences , 2011,
Abstract: To estimate the levels of folic acid and vitamin B12 and their relationship in cigarette smoker with hyperhomocysteinemia. 30 male cigarette smokers in the age group of 30 to 60 years were studied for estimation of serum folic acid, vitamin B12 and total homocysteine (tHcy) over a period of 6 months. These tests were determined by means of Immulite 1000 analyzer. The statistical analysis of smoker group compared with normal control group, showed significant (p<0.001) decreases in serum folic acid, vitamin B12 levels whereas increased concentration of total homocysteine in all 30 smoker subject indicate hyperhomocysteinemia. A positive and significant correlation was observed between folic acid and vitamin B12 in smoker. The present study found a significant association between serum folic acid, vitamin B12 levels and their deficiency in smoker with hyperhomocysteinemia indicate cardiovascular risk in cigarette smoker with hyperhomocysteinemia.
Homocysteine and cardiovascular disease
Hayat Journal of Faculty of Nursing & Midwifery , 2000,
Abstract: "nHyperhomocysteinemia is a condition which , in the absence of kidney disease , indicates a disturpted sulfur amino acid metabolism , either because of vitamin deficiency (folate , B12 and B6 ) or a genetic defect. Epidemiologic"nevidence suggests that mild Hyperhomocysteinemia is associated with increased risk of arteriosclerotic disease and stroke . Hyperhomocysteinemia is an independent risk factor for CHD ."nVitamin therapy with the above vitamins can reduce homocysteine level efficiently.
Hyperhomocysteinemia: Risk factor for development of occlusive vascular diseases  [PDF]
Milo?evi?-To?i? Mirjana,Borota Jela
Medicinski Pregled , 2002, DOI: 10.2298/mpns0210385m
Abstract: Introduction Occlusive vascular diseases take the first places on lists of diseases in general population today. In spite of this, all risk factors which contribute to development of these diseases are not yet known. Recent studies have shown that homocysteine plays a critical role in it and is established as a new risk factor. What is homocysteine? Homocysteine is a sulfur containing amino acid formed in the metabolism of methionine. Reference values of homocysteine in circulation and different forms in plasma are described. Hyperhomocysteinemia - a risk factor Homocysteine was associated with atherosclerosis and occlusive vascular disease in 1960s for the first time. Since then, many studies - prospective and retrospective, have confirmed the role of hyperhomocysteinemia as a risk factor in 42% of patients with cerebrovascular disease, 28% with peripheral vascular and 30% with coronary artery disease. The Physician's Health Study, a prospective study in which 15.000 male physicians took part, revealed that increase in homocysteine concentration of 1.7 μmol/l above normal values was associated by threefold higher risk for myocardial infarction. The risk for carotid artery stenosis also increases with elevation of homocysteine concentration. Hyperhomocysteinemia is associated with poor prognosis in patients with angiographically established coronary disease. Stroke, venous thromboembolism, and atherosclerosis in chronic renal failure are some of the complications of hyperhomocysteinemia. Causes of hyperhomocysteinemia Hyperhomocysteinemia has numerous genetic and nongenetic etiologic factors. Cystationine synthase deficiency, methylentetrahydrofolate reductase deficiency and defects in the synthesis of cobalamin cofactors are genetically determined. Nutritional factors such as B12, folate or B6 vitamin deficiency, cofactors in homocysteine metabolism, lead to hyperhomocysteinemia. Mechanisms of homocysteine action Atherogenic propensity of homocysteine is related to endothelial dysfunction, blood thrombocyte aggregation changes in factors of coagulation. Oxidative stress is involved, but the exact mechanism is still unknown. Conclusion Hyperhomocysteinemia is established as an important risk factor for occlusive vascular diseases. Reduction in homocysteine concentration can be achieved by supplementation of B-group vitamins, cofactors in homocysteine metabolism. Is it going to be effective in reducing cardiovascular risks remains to be seen.
Transient Increase in Homocysteine but Not Hyperhomocysteinemia during Acute Exercise at Different Intensities in Sedentary Individuals  [PDF]
Eduardo Iglesias-Gutiérrez, Brendan Egan, ángel Enrique Díaz-Martínez, José Luis Pe?alvo, Antonio González-Medina, Pablo Martínez-Camblor, Donal J. O’Gorman, Natalia úbeda
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051185
Abstract: Considering that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the purpose of this study was to determine the kinetics of serum homocysteine (tHcy) and the vitamins involved in its metabolism (folates, B12, and B6) in response to acute exercise at different intensities. Eight sedentary males (18–27 yr) took part in the study. Subjects were required to complete two isocaloric (400 kcal) acute exercise trials on separate occasions at 40% (low intensity, LI) and 80% VO2peak (high intensity, HI). Blood samples were drawn at different points before (pre4 and pre0 h), during (exer10, exer20, exer30, exer45, and exer60 min), and after exercise (post0, post3, and post19 h). Dietary, genetic, and lifestyle factors were controlled. Maximum tHcy occurred during exercise, both at LI (8.6 (8.0–10.1) μmol/L, 9.3% increase from pre0) and HI (9.4 (8.2–10.6) μmol/L, 25.7% increase from pre0), coinciding with an accumulated energy expenditure independent of the exercise intensity. From this point onwards tHcy declined until the cessation of exercise and continued descending. At post19, tHcy was not different from pre-exercise values. No values of hyperhomocysteinemia were observed at any sampling point and intensity. In conclusion, acute exercise in sedentary individuals, even at HI, shows no negative effect on tHcy when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate, since no hyperhomocysteinemia has been observed and basal concentrations were recovered in less than 24 h. This could be relevant for further informing healthy exercise recommendations.
Leg ulcers due to hyperhomocysteinemia  [cached]
Krupa Shankar D,Akhib Syed
Indian Journal of Dermatology, Venereology and Leprology , 2006,
Abstract: Chronic leg ulcers are rare in young adults and generally indicate a vascular cause. We report a case of a 26-year-old man with leg ulcers of eight months duration. Doppler study indicated venous incompetence and a postphlebitic limb. However, as the distribution and number of ulcers was not consistent with stasis alone and no features of collagen vascular disease were noted, a hyperviscosity state was considered and confirmed with significantly elevated homocysteine level in the serum. Administration of vitamins B1, B2, B6 and B12, trimethyl-glycine, mecobalamine, folic acid and povidone iodine dressings with culture-directed antibiotic therapy led to a satisfactory healing of ulcers over a period of one month. Hyperhomocysteinemia must be considered in the differential diagnosis of leg ulcers in young individuals.
Homocysteine, vitamin B12 and folate levels in premature coronary artery disease
Saeed Sadeghian, Faramarz Fallahi, Mojtaba Salarifar, Gholamreza Davoodi, Mehran Mahmoodian, Nader Fallah, Soodabeh Darvish, Abbasali Karimi, Tehran Heart Center
BMC Cardiovascular Disorders , 2006, DOI: 10.1186/1471-2261-6-38
Abstract: We performed an analytical case-control study on 294 individuals under 45 years (225 males and 69 females) who were admitted for selective coronary angiography to two centers in Tehran.After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9 micromol/lit, P = 0.01). However there was no significant difference in homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 ± 1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia.We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.Homocysteine is a sulfhydryl containing amino acid produced by demethylation of an essential amino acid (methionine) [1]. Methylation of homocysteine, catalyzed by methionine synthetase produces methionine. This enzyme needs vitamin B12 as a co-factor. Homocysteine can also change to cystathionine through the action of the Cystathionine-B-Synthetase (CBS) enzyme [2,4].In humans, vitamin B12 acts as a coenzyme while folic a
Diabetic Retinopathy and Homocysteine in Newly Diagnosed Type 2 Diabetes Mellitus  [cached]
Md. Rezwanur Rahman,M Iqbal Arslan,Md. Mozammel Hoque,Md. Waliur Rahman
Delta Medical College Journal , 2013, DOI: http://dx.doi.org/10.3329/dmcj.v1i2.15916
Abstract: Background: Diabetic retinopathy is the commonest complication that occurs from the very beginning in patients with diabetes mellitus (DM). DM itself leads to increased homocysteine (Hcy) level. It is postulated that hyperhomocysteinaemia causes retinal vascular damage as Hcy is an established vasculotoxic agent and auto-oxidation of Hcy leads to oxidative stress, endothelial dysfunction, platelet activation and thrombus formation.Objective: The aim of the study was to evaluate the serum Hcy in newly diagnosed type 2 diabetic subjects with diabetic retinopathy.Materials and method: A case control study was carried out in the department of Biochemistry, Bangabandhu Sheikh Mujib Medical University, Dhaka, during the period of January 2006 to December 2007. Total 85 newly diagnosed type 2 diabetic subjects were included in this study, 40 were case having retinopathy and 45 were age and sex matched control without retinopathy. Serum Hcy was measured and compared between case and control.Results: Serum Hcy level in cases was significantly higher (p<0.05) compared to that of control (15.11±5.49 μmol/L vs. 12.59±4.01 μmol/L). Odds ratio was also determined for hyperhomocysteinemia (OR=2.23; CI 0.9-5.45).Conclusion: Hyperhomocysteinaemia is associated with diabetic retinopathy in newly diagnosed type 2 diabetes.
Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children
ON Eldeen, SH Abd Eldayem, RH Shatla, NA Omara, SS Elgammal
Egyptian Journal of Medical Human Genetics , 2012,
Abstract: The relationship between increased homocysteine (Hcy) level and epileptic seizure remains controversial in human, despite a growing evidence of the pro-convulsive effect of the hyperhomocysteinemia (HHcy) observed in the animal studies. The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of homocysteine (Hcy), the cofactors involved in its metabolism as folic acid and vitamin B12 and anti-epileptic drugs (AEDs) in epileptic patients. Serum level of homocysteine (Hcy), folic acid and vitamin B12 was measured in 60 patients with idiopathic epilepsy; and its level was compared to 30 healthy children serving as control group. No significant difference was found regarding the plasma homocysteine (Hcy) levels between patients (both receiving anti-epileptics and non anti-epileptic drug users) and controls. Epileptic patients on polytherapy showed higher mean serum levels of homocysteine (Hcy) and lower mean serum levels of folic acid compared to those on monotherapy. However, the mean serum levels of homocysteine (Hcy), vitamin B12 and folic acid showed non significant differences between patients using valproic acid (VPA) or carbamazepine (CBZ). Duration of AED therapy showed a significant positive correlation with mean serum levels of homocysteine (Hcy) and a significant negative correlation with mean serum levels of folic acid. To conclude; AEDs upset the homeostatic balance of homocysteine (Hcy) and its cofactors and cause abnormalities in their serum levels.
Total plasma homocysteine, folate, and vitamin b12 status in healthy Iranian adults: the Tehran homocysteine survey (2003–2004)/a cross – sectional population based study
Hossein Fakhrzadeh, Sara Ghotbi, Rasoul Pourebrahim, Masoumeh Nouri, Ramin Heshmat, Fatemeh Bandarian, Alireza Shafaee, Bagher Larijani
BMC Public Health , 2006, DOI: 10.1186/1471-2458-6-29
Abstract: This study was a part of the Cardiovascular Risk Factors Survey in the Population Lab Region of Tehran University has been designed and conducted based on the methodology of MONICA/WHO Project. A total of 1214 people aged 25–64 years, were recruited and assessed regarding demographic characteristics, homocysteine, folate, and vitamin B12 levels with interview, questionnaires, examination and blood sampling. Blood samples were gathered and analyzed according to standard methods.The variables were assessed in 1214 participants including 428 men (35.3%) and 786 women (64.7%). Age-adjusted prevalence of hyperhomocysteinemia (Hcy≥15 μmol/L) was 73.1% in men and 41.07% in women (P < 0.0001). Geometric mean of plasma homocysteine was 19.02 ± 1.46 μmol/l in men and 14.05 ± 1.45 μmol/l in women (P < 0.004) which increased by ageing. Age-adjusted prevalence of low serum folate level was 98.67% in men and 97.92% in women. Age-adjusted prevalence of low serum vitamin B12 level was 26.32% in men and 27.2% in women. Correlation coefficients (Pearson's r) between log tHcy and serum folate, and vitamin B12 indicated an inverse correlation (r = -0.27, r = -0.19, P < 0.0001, respectively).These results revealed that the prevalence of hyperhomocysteinemia, low folate and vitamin B12 levels are considerably higher than other communities. Implementation of preventive interventions such as food fortification with folic acid is necessary.Homocysteine (Hcy) is a nonessential sulfur-containing amino acid formed from the demethylation of an essential amino acid, methionine [1]. Plasma folate and vitamin B12 influence homocysteine metabolism as cosubstrate and cofactor, respectively [2]. Elevated plasma total homocysteine (tHcy) has been linked both to the inadequate status of vitamin cofactors (i.e. folate, vitamin B12 and B6) and to genetic defects in enzymes involved in homocysteine metabolism [3]. Genetic causes are mostly defects in the enzymes that control homocysteine metabolism. It is
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