Iranian Journal of

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Introduction: Elevated plasma total homocysteine is an independent risk factor for cardiovascular disease and a sensitive marker of vitamin B12 and folate insufficiency. Folate and vitamin B12 have a protective effect on cardiovascular disease. This effect may be partly explained by mechanisms independent of homocysteine. This survey is the first population based study to evaluate the plasma total homocysteine, folic acid and vitamin B12 in 1214 healthy Iranian persons.
Methods: This study which was a part of the Cardiovascular Risk Factors Survey in the Population Lab region, has been designed and conducted based on MONICA/WHO project. A total of 1214 people have been recruited and assessed on serum homocysteine, folic acid and vitamin B12 with interview, questionnaires, examination and blood sampling. Blood samples were gathered in Venoject tubes and analyzed according to standard methods.
Results: The variables were assessed in 1214 participants include 428 men (35.3%) and 786 women (64.7%). Prevalence of hyperhomocysteinemia was 96.4% in men and 83.3% in women (p<0.0001). Geometric mean of serum homocysteine was 19.02 ± 1.46 µmol/l in men and 14.05± 1.45 µmol/l in women (p<0.004) and increased with age. Folic acid deficiency was seen in 527 (98.9% )men and 833 women (98.0%). 161 (30.1%)men and 232(27.2%) women had vitamin B12 deficiency.
Conclusion: These results revealed that the prevalence of hyperhomocysteinemia, folic acid and vitamin B12 deficiency was higher than other communities considerably. Preventive interventions as food fortification with folic acid is necessary.

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Background: Diabetes mellitus is the most common cause of renal failure, blindness, non- traumatic amputation and neuropathy. Homocysteine, a sulfurated amino acid, has a close correlation with Methionine and Cysteine. The conversion of Methionine to Homocysteine and Cysteine is required coenzymes like vitamin B6, B12 and Folate. The effect of Metformin on serum Homocysteine level by decreasing vitamin B12 level in patients with type 2 diabetes mellitus was described previously. Methods: This is a prospective clinical trail study among patients with type 2 diabetes mellitus in Shiraz. 76 patients were divided into two groups (38 patients in each group). First group treated with Metformin 500-2000 mg/day and the second group treated with Glibenclamide 5-20 mg/day with follow up period of at least 6 months. Hb and MCV were used in follow up to detect megaloblastic anemia, indicator of B12 and folate deficiency. Fasting plasma Homocysteine level Hb A1C and blood sugar were measured in baseline and at 3 and 6 months follow up periods. Results: There was no significant difference between age, sex, weight, height and BMI and baseline serum profile between the two groups. Homocysteine level increased significantly in Metformin group at 3 and 6 months(P=0.003 and 0.001 respectively). Mean plasma homocysteine level after 6 months were 10.98±0.58 μmol/l in Metformin and 10.0± 0.88 μmol/l in Glibenclamide group, with significant difference between the two groups (P=0.001). Conclusion: Metformin increases the plasma Homocysteine level. Metformin will accumulate highly in gastrointestinal wall and cause malabsorption of vitamin B12, therefore we can conclude that the use of Metformin for 6 months can cause vitamin B12 malabsorption and increase in plasma homocysteine level. Increase in plasma homocysteine level was 7.54% in our study that is higher in comparing to the other studies. It can be explained by longer duration of Metformin therapy in our study. Rising in Homocysteine levels may have detrimental effect on vessels that need further study.

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Background: Homocysteine is regarded as a risk factor for metabolic syndrome and cardiovascular diseases. It is of great importance to determine exact risk factors of these disorders because of their high prevalence.
Methods: The 25-64 year old individuals in 17th district of Tehran were studied. It was designed according to the WHO MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) project using the ATP III criteria. Homocysteine levels higher than 15 µmol/l and Folate and vitamin B12 lower than 11 nmol/l and 185 pmol/l, respectively were considered as abnormal.
Results: Of the whole population, prevalence of abnormal homocysteine, Folic acid and vitamin B12 was 54.5%, 98.2% and 27%, respectively. Homocysteine levels were higher in men than women (P= 0.026). None of the differences between the means of these three risk factors were statistically significant in people with and without the metabolic syndrome. The only significant difference was higher homocysteine levels in women with metabolic syndrome (P= 0.010).
Conclusions: According to this study, hyperhomocysteinemia and Folate and vitamin B12 deficiency are more prevalent in our population. But there was no correlation between these factors and risk of metabolic syndrome. Because of the controversy about this issue and high prevalence of cardiovascular diseases in our country, further studies are suggested.

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Background: Homocysteine is one of the novel cardiovascular risk factors. We know most of the cardiovascular and diabetes risk factors are accompanied. The aim of this study was to determine the role of homocysteine in diabetes.
Methods: The study was performed in 25-64 year old individuals of the 17th district of Tehran according to WHO MONICA project. Homocysteine levels higher than 15 µmol/l was considered as abnormal. According to ADA 2004 criteria, fasting glucose levels of 100 to 125 mg/dl were considered as impaired glucose tolerance (IGT), while levels higher than 125 mg/dl included diabetes.
Results: Prevalence of hyperhomocysteinemia was 54.5% in the whole population. Prevalence of IGT and diabetes were 3.5% and 10.1%, respectively. There was no difference between prevalence of IGT and diabetes in both hyperhomocysteinemic and normal group (P= 0.365). The difference was also not significant in each genders, but mean glucose levels were significantly lower in people with hyperhomocysteinemia (P= 0.003).
Conclusion: This study emphasizes that an inverse relation between glucose and homocysteine levels. Some studies indicate an opposite result and there is controversy on it. More researches may determine the exact role of homocysteine in diabetes.

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Background: Hyperhomocysteinemia may increase blood pressure by inducing endothelial cells dysfunction . The aim of this study was determining the relationship between plasma Homocysteine (Hcy) levels and blood pressure in new cases of type 2 diabetes mellitus.
Methods: As a cross sectional study, 46 new cases of type 2 diabetes mellitus referred to Isfahan Endocrine and Metabolism Research Center were selected by convenient sampling. Basal characteristics of patients were recorded. Systolic and diastolic blood pressure was measured two times with 30 minutes interval on two consequent days. After ten hours of overnight fasting, blood samples were taken to measure fasting plasma glucose, HbA1c, triglyceride, Total cholesterol, HDL-C and creatinine. All data were expressed as mean (SD). Relationship between plasma Homocysteine levels and both systolic and diastolic blood pressure was assessed by Pearson's correlation coefficient. Patients were divided into three groups according to their plasma Homocysteine levels, (Hcy<10mol/L, 10Hcy<15 mol/L and Hcy15mol/L).. Then mean of systolic and diastolic blood pressure between groups were compared by one – way ANOVA and Tuckey-HSD tests.
Results: Mean (SD) of plasma Homocysteine levels was 12.2 (6.8) mol/L and of systolic and diastolic blood pressure was 128.8 (18.1) and 82.3(9) mm/Hg, respectively. There was a significant correlation between plasma Homocysteine levels, and both systolic (r=0.39, P<0.01) and diastolic (r=0.46, P<0.01) blood pressures. Mean (SD) of systolic and diastolic blood pressure in patients with plasma Homocysteine level of 15mol/L was 152.5 (17.7) and 91.8 (7.3) mm/Hg, respectively, so blood pressure in those group with hyperhomocysteinemia was higher than other two groups (P<0.001). There was no correlation between Homocysteine levels and FPG, HbA1c and lipid profile.
Conclusion: There is a significant correlation between plasma Homocysteine levels and both systolic and diastolic blood pressure in newly diagnosed type 2 diabetics. Patients with hyperhomocyteinemia have higher blood pressure.

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Background: Elevated total plasma Homocysteine, is an independent risk factor for cardiovascular disease. Folate and vitamin B12 have not only a protective effect on cardiovascular disease but also an essential effect on total Homocysteine concentrations (tHcy). This survey has been conducted to evaluate the determinants of tHcy in 1191 healthy Iranian adults.
Methods: This study which was a part of the Cardiovascular Risk Factors Survey in the Population Lab Region, has been designed and conducted based on MONICA/WHO project. A total of 1191 people have been recruited and assessed on serum Homocysteine, Folic acid and vitamin B12, triglycerides, cholesterol, HDL-C, LDL-C, FBS, BMI, BP and smoking, with interview, questionnaires, examination and blood sampling. Blood samples were analyzed according to standard methods.
Results: The variables were assessed in 1191 participants include 416 men (34.9%) and 775 women (65.1%). Prevalence of hyperhomocysteinemia was correlated significantly with male sex and aging. Hcy levels were inversely related to serum Folate and vitamin B12 concentrations. After further adjustments, we detected a positive correlation between tHcy and age, male sex, smoking and BMI, and a negative one with LDL-C and diabetes. Although there was a correlation between tHcy and blood pressure, after age, sex, BMI and smoking adjustment, it just remained significant in women and with systolic blood pressure.
Conclusion: We found that dietary and lifestyle parameters such as Folate intake and smoking habit are the main determinants of distribution of plasma Homocysteine in an apparently healthy population. We assumed that lifestyle changes could have considerable subsequences in public health. Our findings confirm the potential advantages of dietary improvements and increased intake of nutrients along with smoking cessation in order to prevent cardiovascular diseases in high-risk patients.

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Background: Fortification of corn with folic acid has beneficial effects on hyperhomocysteinemia and heart disease. Folate fortification was contributed to an increase in average folate status and a reduction in serum homocysteine concentration.

Methods: In this randomized clinical trial 17 men and women aged 61±5 years old with hyperhomocysteinemia with mean homocysteine concentration of 15/32±6/13 µmol/L were recruited. Subjects received fortified bread which contained 100µg folic acid daily for 8 weeks. Three-day food record, food frequency questionnaire and BMI (Body Mass Index) data at baseline and week 8 were completed. Plasma homocysteine and serum folate at baseline and week 8 were measured. All dietary and statistical analyses were undertaken using Nutritionist III and SPSS release 15.0 software with paired t-test.

Results: Mean plasma homocysteine concentration decreased significantly in hyperhomocysteinemic subjects after daily consumption of folate fortified bread for 8 weeks (P<0.001).After 8 weeks serum folate concentration increased %26 (P=0.06). Mean BMI, energy and other components of dietary intake did not change significantly. Dietary vitamin C decreased significantly (P<0.001).

Conclusion: Daily consumption of folic acid fortified bread, with 100 µg folic acid, in hyperhomocysteinemic subjects for 8 weeks led to significant decrease in plasma homocysteine and an increase in serum folate.

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High plasma homocysteine is identified as an important risk factor for cardiovascular disease. Epidemiological studies have shown that increased plasma homocysteine is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease. Homocysteine may have an effect on atherosclerosis by damaging the inner lining of arteries and promoting blood clots .Folic acid and other B group vitamins help break down homocysteine in the body and folate fortification of foods reduces the average homocysteine level in the population. Low blood levels of folate are also linked with a higher risk of fatal coronary heart disease and stroke. Homocysteine levels are strongly influenced via diet, as well as via genetic factors. Many common genetic disorders and problems (such as vitamin deficiency) adversely affect the metabolism of homocysteine. Common causes of a high homocysteine level include dietary deficiency of folate and B group vitamins, hypothyroidism, kidney disease, psoriasis, and some medicines. Clinical trials to date have not provided consistent evidence that lowering homocysteine levels reduce strokes, heart attacks and other cardiovascular events notwithstanding it is recommended to lower a high homocysteine level because it is a risk factor for heart disease. Homocysteine abnormalities also contribute to birth defects and dementia and folic acid supplementation in the pre-conceptual period is effective in preventing recurrent and primary neural tube defects.

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Background: Diabetes is the most common metabolic diseases and its vascular complications are main cause of death in diabetic patients. Patients with hyperglycemia, dyslipidemia and oxidative stress are prone to diabetes complications. The goal of this study was investigation of the effect of cysteine (Cys) on hyperglycemia, lipid profile, atherogenic index, glyoxal, methylglyoxal, oxidative stress and, glycation and oxidation of LDL in the rat model of diabetes –atherosclerosis. Methods: Diabetes was induced in the rats using Streptozotocin injection then they put on the atherogenic diet. The groups under study were including of control and diabetic rats, and two other similar groups under Cys (0.05 % in dirking water) treatment. After one month, fasting blood sugar (FBS), lipid profile, atherogenic index (LDL/HDL), glycated and oxidized LDL, AGEs, glyoxal, methylglyoxal, Advanced oxidation protein products (AOPP) as an oxidative stress index and weight of rat was measured. Results: Diabetic-atherosclerotic rat groups significantly showed higher level of FBS, triglyceride, cholesterol, LDL, atherogenic index, glycated and oxidized LDL, glyoxal, methylglyoxal and AOPP than control group. These parameters significantly (P < 0.001) reduced in diabetic group treated with Cys in comparison of untreated. Conclusion: Cysteine with improving property on glycemic and lipemic conditions, inhibitory activity on glycation and oxidation of LDL and reduction of oxidative stress in diabetic-atherosclerotic rats could recommended as a drug for prevention of diabetes complications.

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Background: The purpose of this study was to investigate the effect of eight weeks of aerobic exercise and supplementation of gensing on homocysteine levels, tiroid hormon and insulin resistant in obese women with hypothyroidism.
Methods: This study is quasi-experimental study. For this purpose, 40 obese women with hypothyroidism with an average age of 34.62 ± 3.55 years, weight 80.47 ± 3.85 kg and BMI of 32.2 ± 2.27 kg / m2, were randomly divided into four groups including aerobic training (10), ginsing (10), aerobic exercise and ginsing (10) and placebo (10) were divided.Aerobic exercise included 8 weeks of aerobic training, 3 sessions per week, 45 to 70 minutes, and 55 to 75% of maximum heart rate. Patients in the ginseng group and aerobic exercise with ginsing consumed each day a Jinsen's capsule containing 250 mg of granule Risomy ginseng powder was taken orally after 8 weeks for 8 weeks, while subjects in the placebo group received flour powdered capsules.Blood samples from the anterior vein were used to measure homocysteine, TSH, T3, T4, glucose and insulin before and after 8 weeks in four groups. For data analysis, dependent t-test and variance analysis were used (P≤0/05).
Results: The results showed that the plasma homocysteine, TSH, glucose concentrate, insulin resistance and insulin resistance were significantly decreased in all three experimental groups while T3 and T4 increased (P <0.05). These indices in the control group were not changed (P <0.05).
Conclusion: Therefore, aerobic exercise, along with supplementation with ginsing, can have an important role in preventing an increase in cardiovascular risk factors and hypothyroidism in obese women with hypothyroidism.