Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homocysteine (Hcy) may represent a metabolic link in the pathogenesis of atherosclerotic vascular diseases and old-age dementias. Hyperhomocysteinemia is an independent risk factor for coronary artery disease and peripheral vascular disease, and is also associated with cerebrovascular disease; specifically, the risk of extracranial carotid atherosclerosis significantly increases in relation to Hcy levels. Hcy is a reliable marker of vitamin B12 deficiency, a common condition in the elderly which is known to induce neurological deficits including cognitive impairment; a high prevalence of folate deficiency has been reported in psychogeriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAMe), a major methyl donor in CNS; therefore, deficiencies in either of these vitamins lead to a decrease in SAMe and increase in Hcy, which can be critical in the aging brain. Another pathogenetic mechanism linking high Hcy levels to reduced cognitive performances in the elderly might be represented by excitotoxicity, since hyperhomocysteinemia may lead to an excessive production of homocysteic acid and cysteine sulphinic acid, which act as endogenous agonists of NMDA receptors. Considering the reasonably high prevalence in the general population of a genetic predisposition to a thermolabile form of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), hyperhomocysteinemia can be seen as the result of multiple genetic and environmental factors leading to vascular and/or neurodegenerative disorders where age-related involutive phenomena represent a common pathogenetic ground. Systematic studies in different psychogeriatric conditions monitoring Hcy levels and clinical features before and after vitamin supplementation are therefore highly recommended.
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PMID:Role of homocysteine in age-related vascular and non-vascular diseases. 935 35

Because of the large liver stores (about 5 mg), low turnover rate (0.143%) and small daily requirement (3 micrograms), vitamin B12 deficiency does not occur under normal circumstances. This is not the case in individuals with chronic inflammatory or trophic changes at vitamin B12 absorption sites. Without supplementation, vitamin B12 deficiency can be expected within 5 years of gastrectomy. Characteristic features of type A gastritis are hyposecretion and mucosal atrophy in the fundus and body of the stomach, with absent intrinsic factor. In the small intestine, active and/or passive absorption is impaired by extensive ileal resection, exocrine pancreatic insufficiency and chronic inflammatory disorders such as Crohn's disease. Definitive plasma concentrations cannot be quoted for vitamin B12 deficiency. Dietary habits, subjective symptoms, hematological laboratory results, function tests and gastrointestinal endoscopic and histological findings must all be taken into account in the diagnosis. Modern diagnostic parameters, such as methylmalonic acid and homocysteine serum assays, are useful for achieving early diagnosis and hence optimal treatment. With their assured availability, parenteral vitamin B12 preparations remain the treatment of choice. Results from vitamin B12 bioavailability studies in healthy subjects suggest that > 300 micrograms probably suffices as an oral maintenance dose after parenteral loading. Further well-documented cases are needed in order to establish whether these doses are adequate in malabsorption syndromes and gastrointestinal diseases. Various case reports indicate the value of prophylactic and therapeutic oral vitamin B12 administration, especially in disorders of homocysteine metabolism, a substance postulated as a further important risk factor for atherosclerosis.
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PMID:Studies on vitamin B12 status in the elderly--prophylactic and therapeutic consequences. 1038 32

We review the beneficial and adverse effects of vegetarian diets in various medical conditions. Soybean-protein diet, legumes, nuts and soluble fibre significantly decrease total cholesterol, low-density lipoprotein cholesterol and triglycerides. Diets rich in fibre and complex carbohydrate, and restricted in fat, improve control of blood glucose concentration, lower insulin requirement and aid in weight control in diabetic patients. An inverse association has been reported between nut, fruit, vegetable and fibre consumption, and the risk of coronary heart disease. Patients eating a vegetarian diet, with comprehensive lifestyle changes, have had reduced frequency, duration and severity of angina as well as regression of coronary atherosclerosis and improved coronary perfusion. An inverse association between fruit and vegetable consumption and stroke has been suggested. Consumption of fruits and vegetables, especially spinach and collard green, was associated with a lower risk of age-related ocular macular degeneration. There is an inverse association between dietary fibre intake and incidence of colon and breast cancer as well as prevalence of colonic diverticula and gallstones. A decreased breast cancer risk has been associated with high intake of soy bean products. The beneficial effects could be due to the diet (monounsaturated and polyunsaturated fatty acids, minerals, fibre, complex carbohydrate, antioxidant vitamins, flavanoids, folic acid and phytoestrogens) as well as the associated healthy lifestyle in vegetarians. There are few adverse effects, mainly increased intestinal gas production and a small risk of vitamin B12 deficiency.
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PMID:Vegetarian diet: panacea for modern lifestyle diseases? 1087 92

Values of homocysteine and lipid parameters were measured in groups of adults consuming alternative nutrition (vegetarians/lactoovo/, vegans) and compared with a group consuming traditional diet (omnivores, general population). Frequency of hyperhomocysteinemia was 53% in the vegans group, 28% in vegetarians vs. 5% in omnivores. In conditions of lower methionine intake (reduced content in plant proteins), the remethylation pathway of homocysteine metabolism prevails and it is vitamin B12 and folate-dependent. The intake of vitamin B12 is equal to zero in vegans; vegetarians consume 124% of the RDA vs. 383% in omnivores. Serum vitamin levels are significantly lower in subjects consuming alternative nutrition with deficiency observed in 24% of vegetarians, 78% of vegans vs. 0% in omnivores. Serum folate levels are within the reference range in all groups. Mild hyperhomocysteinemia in the groups consuming alternative diet is a consequence of vitamin B12 deficiency. Vegetarians and vegans meet the RDA for energy and fat, and have a favourable proportion of saturated, mono- and polyunsaturated fatty acids on total energy intake; the ratio of linoleic/alpha-linolenic acid in their diet corresponds with the recommendations. They have low cholesterol consumption and higher vitamin E and C intake. Optimal fat intake of correct composition is reflected in lower values of atherosclerosis risk factors (cholesterol, LDL-cholesterol, atherogenic index, saturated fatty acids, triacylglycerols), and significantly higher levels of protective substances (linoleic acid, alpha-linolenic acid, HDL-cholesterol, vitamin E, vitamin E/cholesterol, vitamin C). Low lipid risk factors but higher findings of mild hyperhomocysteinemia in vegetarians mean a diminished protective effect of alternative nutrition in cardiovascular disease prevention.
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PMID:Traditional and alternative nutrition--levels of homocysteine and lipid parameters in adults. 1121 48

Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.
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PMID:Vitamin B12 deficiency. 1476 65

Since the adoption of vegetarian diets as a healthy lifestyle has become popular, the cardiovascular effects of long-term vegetarianism need to be explored. The present study aimed to compare the presence and severity of carotid atherosclerosis (CA), and the blood levels of Vitamin B12, homocysteine (Hcy) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between 57 healthy postmenopausal vegetarians and 61 age-matched omnivores. Carotid atherosclerosis, as measured by ultrasound, was found to be of no significant difference between the two groups. Yet, fasting blood glucose, low-density lipoprotein cholesterol, and Vitamin B12 were significantly lower, while Hcy and sVCAM-1 were higher in the vegetarians as comparing with the omnivores. Multivariate regression analysis showed that the level of Vitamin B12 was negatively associated with the level of Hcy. Vegetarianism itself and Hcy level were significantly associated with sVCAM-1 level in univariate analysis; however, after adjustment for covariates, we identified age but not vegetarianism as the determinant of sVCAM-1 level. Multiple linear regression analysis identified age and systolic blood pressure, but not vegetarianism, as determinants of common carotid artery IMT. In conclusion, there was no significant difference in CA between apparently healthy postmenopausal vegetarians and omnivores. The findings of elevated Hcy in vegetarians indicate the importance of prevention of Vitamin B12 deficiency.
Atherosclerosis 2006 Feb
PMID:Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores. 1600 9

Vegetarians have a lower intake of vitamin B12 than omnivores do. Vitamin B12 deficiency (holotranscobalamin II <35 pmol/L or methylmalonic acid >271 nmol/L) was found in 58% of 71 vegetarians studied. Higher homocysteine levels (>12 micromol/L) found in 45% indicate disturbed remethylation of homocysteine to methionine. The methylation of DNA is strongly linked to homocysteine metabolism. Since DNA methylation is an important epigenetic factor in the regulation of gene expression, alteration of the methylation pattern has been associated with aging, cancer, atherosclerosis and other diseases. Three observations indicate that DNA methylation could be diminished by a vegetarian lifestyle. The vegetarian diet has a low content of methionine, remethylation of homocysteine is reduced by vitamin B12 deficiency and elevated homocysteine levels can induce the generation of S-adenosylhomocysteine (SAH), a potent inhibitor of methyltransferases. In our study we observed a significant correlation between SAH and whole-genome methylation (r=-0.36, p<0.01). This observation underlines the role of SAH as a potent inhibitor of methyltransferases. The methylation status was not correlated with homocysteine or S-adenosylemethionine (SAM). These results indicate that the degree of methylation does not depend on the supply of methyl groups and that the reverse generation of SAH has no influence. In addition to whole-genome methylation, the specific promoter methylation of the p66Shc gene was studied. However, the latter did not correlate with SAH, SAM or homocysteine. Obviously, the promoter methylation of the p66Shc gene is controlled in a specific way, without following the general regulating influence of SAH. In conclusion, an inhibitory effect of SAH on whole-genome methylation was found, but from our data no interaction between vegetarian lifestyle and DNA methylation could be determined.
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PMID:The vegetarian lifestyle and DNA methylation. 1619 15

A 27 year-old man who presented to the hospital with progressive lower extremity weakness, developed an acute ST elevation myocardial infarction on his second hospital day. Primary angioplasty to the left anterior descending coronary artery was performed. Due to persistent dyspnea, the patient underwent a diagnostic chest computed tomography which confirmed multiple small pulmonary emboli. Laboratory analysis revealed a megaloblastic anemia with a reduced vitamin B12 level and positive titers for antibodies against intrinsic factor, establishing a diagnosis of pernicious anemia. Screening for hypercoaguable markers documented an isolated severely elevated homocysteine levels (105 mumol/l). No other significant risk factors for coronary artery disease including a family history of premature atherosclerosis were identified. This case illustrates the importance of testing for hyperhomocysteinemia as part of a workup for atherothrombotic disease, especially in patients without other significant risk factors. The severity of hyperhomocysteinemia found in our patient is unusual for patients with vitamin B12 malabsorption and raises the question of whether the widely practiced folic acid fortification in the United States may mask or even worsen vitamin B12 deficiency over time, leading to more severe cases of vitamin B12 deficiency and hyperhomocysteinemia than seen in the past.
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PMID:Acute myocardial infarction and pulmonary embolism in a young man with pernicious anemia-induced severe hyperhomocysteinemia. 1943 95