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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses research methodology in the relation between diet and disease. Medical research can be divided into two types: complex research (the detailed study of disease mechanisms using such methods as biochemistry and molecular genetics) and simple research (the investigation of the factors that cause or prevent disease using methods such as epidemiology, intervention trials, and analagous studies on animals). Although complex research has received the bulk of resources, the large majority of our information of practical value has come from simple research. This general principle is illustrated in the area of diet and disease by examples from various areas: selenium, carotenoids, and cancer; vitamin E, omega-3 fatty acids, and coronary heart disease; dietary fat and obesity; dietary sodium and hypertension; and alcohol and stroke. Discussion then turns to aspects of the design of cohort (prospective) studies. Because of problems of sample size and relative lack of diversity, previous studies often failed to give clear-cut results. Suggestions are made concerning the design of cohort studies, notably the use of much larger numbers of subjects and with greater diversity in their diets. The problem of confounding also is discussed. Lifestyle factors often cluster together but cohort studies may not have fully unraveled this.
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PMID:Nutrition and disease: challenges of research design. 1193 52

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.
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PMID:The HOPE Study (Heart Outcomes Prevention Evaluation). 1196 89

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of atherosclerosis, arterial hypertension and non-insulin-dependent diabetes mellitus. The aim of the study was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), products of cholesterol peroxidation--oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese women without coexisting diseases. The study was performed in 11 morbidly obese women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31 kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs. 0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs. 41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/- 199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control group, while there were no significant differences between the two groups in concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG) ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p < 0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p < 0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover, concentration of 7-K correlated positively with the level of HDL (r = 0.54; p < 0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there are disturbances in cholesterol peroxidation processes, with the rise in oxysterol levels and the decrease in vitamin E concentration in lipoproteins, which may be involved in the increased incidence of cardiovascular diseases in morbidly obese women.
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PMID:[Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly obese women]. 1199 10

Caffeine is the most widely consumed behaviourally active substance in the western world. Neuroprotective effects of caffeine in low doses, chronically administered, have been shown in different experimental models. If caffeine intake could protect against neurodegeneration in Alzheimer's disease (AD), then higher levels of caffeine consumption in normal subjects as compared with AD patients should be detectable in the presumably long period before diagnosis when insidious pathogenic changes are taking place. A case-control study was used: cases were 54 patients with probable AD fulfilling the National Institute of Neurologic and Communicative Disorders and Stroke and the AD and Related Disorders Association criteria, in a Dementia Clinics setting. Controls were 54 accompanying persons, cognitively normal, matched for age (+/-3 years) and sex. Patients with AD had an average daily caffeine intake of 73.9 +/- 97.9 mg during the 20 years that preceded diagnosis of AD, whereas the controls had an average daily caffeine intake of 198.7 +/- 135.7 mg during the corresponding 20 years of their lifetimes (P < 0.001, Wilcoxon signed ranks test). Using a logistic regression model, caffeine exposure during this period was found to be significantly inversely associated with AD (odds ratio=0.40, 95% confidence interval=0.25-0.67), whereas hypertension, diabetes, stroke, head trauma, smoking habits, alcohol consumption, non-steroid anti-inflammatory drugs, vitamin E, gastric disorders, heart disease, education and family history of dementia were not statistically significantly associated with AD. Caffeine intake was associated with a significantly lower risk for AD, independently of other possible confounding variables. These results, if confirmed with future prospective studies, may have a major impact on the prevention of AD.
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PMID:Does caffeine intake protect from Alzheimer's disease? 1209 22

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of arterial hypertension and non-insulin dependent diabetes mellitus. The aim of the study was to assess plasma concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG) and two parameters of oxidation stress--vitamin E and oxysterols, in morbidly obese patients with coexisting arterial hypertension and non-insulin dependent diabetes mellitus. Studies were performed in 37 morbidly obese patients divided into three groups: group I--without coexisting diseases, group II--with arterial hypertension, and group III--with arterial hypertension and non-insulin dependent diabetes mellitus. In all groups there was an increase in TG concentration, a decrease in HDL-cholesterol level, and normal values of TC and LDL-cholesterol. The concentrations of 7-hydroxycholesterols (7-OH) in group II (602.65 +/- 264.46 ng/ml) and group III (570.94 +/- 210.59 ng/ml) were significantly higher compared to that in group I (336.09 +/- 220.74 ng/ml). There were no differences between groups in concentrations of 7-ketocholesterols (7-K), TC, HDL-cholesterol, LDL-cholesterol, TG, vitamin E and vitamin E/(TC + TG) ratio. In all groups TC concentration correlated positively with TG concentration, and negatively with vitamin E/(TC + TG) ratio. Moreover, the positive correlation between TG and HDL-cholesterol concentrations, and negative correlation between plasma vitamin E and 7-K concentrations were demonstrated. In conclusion, although the study demonstrates similar disturbances in lipid profile and oxidation stress parameters in all groups, with significant differences in 7-OH only, the role of cholesterol oxidation products in pathogenesis of arterial hypertension and non-insulin dependent diabetes mellitus in morbidly obese patients cannot be excluded.
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PMID:[Assessment of plasma lipid profile oxysterols and vitamin E concentration in morbidity obese patients with coexisting arterial hypertension and non-insulin dependent diabetes mellitus]. 1210 69

An imbalance between production of reactive oxygen species (ROS) and antioxidant defense is involved in the pathogenesis of diverse chronic parenchymatous diseases. To identify the primary site of such increased oxidative stress, a lipophilic ROS-sensitive probe (C11-Bodipy 581/591) is introduced, which allows the visualization and quantification of oxidative injury using confocal fluorescence microscopy in living cells. The properties of this probe are such that its emission wavelength irreversibly shifts from red to green upon oxidation. This probe was used to identify the spatiotemporal distribution of lipid peroxidation in the rat kidney during chronic NOS inhibition, a model associated with hypertension and proteinuria. Chronic NOS inhibition resulted in increased lipid peroxidation in renal tubules but hardly any in glomeruli or blood vessels. This peroxidation preceded the loss of renal function characteristic of the model and was accompanied by parallel changes in thiobarbituric acid reactive substances in the renal cortex. Furthermore, the increase in oxidation was dependent on angiotensin II and NADPH oxidase and prevented by vitamin E. Induction of cytoprotective heat-shock protein 70 preceded lipid peroxidation, rise in BP, or proteinuria. These findings challenge the paradigm that the vascular wall is the source and target of oxidative stress in chronic parenchymatous renal disease associated with hypertension.
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PMID:Visualizing tubular lipid peroxidation in intact renal tissue in hypertensive rats. 1244 19

This triple-blind placebo-controlled clinical trial was performed to determine the effects of the anti-oxidant vitamin E on blood pressure and heart rate in patients with mild hypertension. A total of 70 new mild hypertensive subjects (systolic blood pressure, SBP: 140-160 mmHg; diastolic blood pressure, DBP: 90-100 mmHg) without secondary hypertension were selected from among people referred to the Hypertension Unit of Isfahan Cardiovascular Research Center and divided randomly into two groups of drug (DG) and placebo (PG). All subjects were aged from 20 to 60 years old, without any other cardiovascular risk factors. The drug group received vitamin E tablets (200 IU/day) and the placebo group received placebo only for 27 weeks. At the beginning and the end of the study, the blood vitamin E level was measured fluorimetrically in all subjects according to the Hansen and Warwick method [14, 15]. Blood pressure and heart rate were measured at the beginning, during, and at the end of the study. Blood pressure was measured by a physician using one random zero mercury sphygmomanometer. Personal information and dietary habits of subjects were collected by separate questionnaire. At the end of the study, it was found that the vitamin E supplement had caused a remarkable decrease in SBP (-24% in DG versus -1.6% in PG) and a less remarkable decrease in DBP (-12.5% in DG versus -6.2% in PG) (p < 0.05). The change in heart rate was -4.3% in DG, and -14.0% in PG (p < 0.05). It is concluded that a vitamin E supplement of 200 IU/day can be effective in mild hypertensive patients in the long term, probably due to nitric oxide, and improve their blood pressure status. Therefore, vitamin E supplement could be recommended to such patients.
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PMID:Vitamin E can reduce blood pressure in mild hypertensives. 1246 6

Serum vitamin C has been inversely associated with blood pressure in several epidemiologic studies, but little is known about effect of other antioxidant vitamins. We examined the relation between serum vitamins A, C, and E, alpha-carotene, and beta-carotene levels and blood pressure among 15 317 men and women > or =20 years of age who participated in the Third National Health and Nutrition Examination Survey. Blood pressure was characterized as the average of 6 measurements obtained over 2 visits by trained observers and hypertension was defined as blood pressure > or =140/90 mm Hg and/or taking antihypertensive medications. In multivariate models, a 1 SD difference in vitamin A (16.2 microg/dL) and vitamin E (20.4 microg/dL) was associated with a 43% (OR, 1.43; 95% CI, 1.34 to 1.53) and 18% (OR, 1.18; 95% CI, 1.09 to 1.27) higher odds of hypertension, respectively. A 1 SD difference in alpha-carotene (0.47 micro g/dL) and beta-carotene (496 microg/dL) was associated with a 16% (OR, 0.84; 95% CI, 0.76 to 0.94) and 11% (OR, 0.89; 95% CI, 0.82 to 0.97) lower odds of hypertension, respectively. In addition, serum vitamins A and E were positively and significantly associated with both systolic and diastolic blood pressure, whereas alpha-carotene and beta-carotene were inversely and significantly associated with systolic and vitamin C associated with diastolic blood pressure in multivariate linear regression analyses. These findings indicate that antioxidant vitamins may be important in the underlying cause and prevention of hypertension. Further studies in this important area are warranted.
Hypertension 2002 Dec
PMID:Serum antioxidant vitamins and blood pressure in the United States population. 1246 62

In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents fructose-induced hypertension by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether dietary supplementation of vitamin E and vitamin C which are known to increase tissue glutathione, a storage form of cysteine, prevents this hypertension and its associated biochemical and histopathological changes. Starting at 7 weeks of age, animals were divided into four groups of six animals each and treated as follows: control group, normal diet and normal drinking water; fructose group, normal diet and 4% fructose in drinking water; fructose + vitamin E group, diet supplemented with vitamin E (34 mg/ kg feed) and 4% fructose in drinking water; fructose + vitamin C group, diet supplemented with vitamin C (1,000 mg/kg feed) and 4% fructose in drinking water. At 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugates were significantly higher in the fructose group. These animals also displayed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin E and C supplementation in fructose-treated WKY rats prevented the increase in systolic blood pressure by normalizing cytosolic [Ca2+]i and kidney and aortic aldehyde conjugates and preventing adverse renal vascular changes.
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PMID:Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats. 1248 32

Antioxidant vitamins C and E have protective properties in genetic hypertension associated with enhanced oxidative stress. This study investigated whether vitamins C and/or E modulate vascular function by regulating enzymatic activities of endothelial nitric oxide synthase (eNOS) and NAD(P)H oxidase using thoracic aortas of 20- to 22-week-old male spontaneously hypertensive rats (SHR) and their matched normotensive counterparts, Wistar-Kyoto rats (WKY). SHR aortas had impaired relaxant responses to acetylcholine but not to sodium nitroprusside, despite an approximately 2-fold increase in eNOS activity and NO release. The levels of superoxide anion (O2-), a potent NO scavenger, and NAD(P)H oxidase activity were also 2-fold higher in SHR aortas. Mechanical but not pharmacological inactivation of endothelium (by rubbing and 100 micromol/L L-NAME, respectively) significantly abrogated O2- in both strains. Treatments of SHR aortas with NAD(P)H oxidase inhibitors, namely diphenyleneiodinium and apocynin, significantly diminished O2- production. The incubation of SHR aortas with different concentrations of vitamin C (10 to 100 micromol/L) and specifically with high concentrations of vitamin E (100 micromol/L) improved endothelial function, reduced superoxide production as well as NAD(P)H oxidase activity, and increased eNOS activity and NO generation in SHR aortas to the levels observed in vitamin C- and E-treated WKY aortas. Our results reveal endothelial NAD(P)H oxidase as the major source of vascular O2- in SHR and also show that vitamins C and E are critical in normalizing genetic endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities.
Hypertension 2003 Mar
PMID:Vitamins reverse endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities. 1262 55


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