Sesame oil and vitamin E co-administration may improve cardiometabolic risk factors in patients with metabolic syndrome: a randomized clinical trial.

OBJECTIVES: Metabolic syndrome (MetS) represents a clustering of metabolic abnormalities that are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to evaluate the effects of sesame oil enriched with vitamin E (vit E), sesame oil alone and sunflower oil on lipid profile, fasting blood glucose (FBG), malondialdehyde (MDA), high-sensitivity C-reactive protein (Hs-CRP), homeostatic model assessment (HOMA-IR), and blood pressure (BP) in patients with MetS. SUBJECTS: Overall, 75 individuals with MetS (aged 30-70 years) participated in this randomized, single-blind controlled trial. Patients were randomly allocated to: (1) Group A (n = 25): sesame oil (30 ml/day) enriched with vit E (400 mg/day), (2) Group B (n = 25): sesame oil (30 ml/day), (3) Group C (n = 25): sunflower oil (30 ml/day). Anthropometric data, dietary intake, blood pressure, and biochemical markers, including fasting serum lipids, FBG, serum insulin, MDA, and hs-CRP were measured at baseline and at week 8. RESULTS: In individuals in the sesame oil enriched with vit E group (Group A), there were significant reductions in serum total cholesterol (TC), triglycerides (TG), FBG, HOMA-IR, MDA, hs-CRP, high-density lipoprotein (HDL-C) systolic and diastolic BP (for all the comparison p < 0.02). Similarly, in Group B (taking sesame oil alone), TC, TG, FBG, HOMA-IR, MDA, systolic and diastolic BP were significantly improved (for all the comparison p < 0.025), while there were no significant changes in serum HDL (baseline = 35.9 ± 7.2 mg/dL vs. 36.4 ± 6.2 mg/dL, p = 0.432) and hs-CRP (baseline = 4.38 ± 1.34 mg/dL vs. week 8 = 3.96 ± 1.7 mg/dL, p = 0.057) in second group. No significant changes in any of the studied clinical and anthropometric data were found in Group C (on sunflower oil). CONCLUSION: Sesame oil (±vit E) was shown to beneficially affect several cardiometabolic indices (including lipids, FBG, BP, HOMA-IR, and MDA) in patients with MetS.

The effect of electro-acupuncture on pro-oxidant antioxidant balance values in overweight and obese subjects: a randomized controlled trial study.

Objective To undertake a randomized controlled trial in 196 obese subjects to examine the effect of electro-acupuncture on serum pro-oxidant antioxidant balance (PAB) values. Methods Subjects received authentic acupuncture (cases) or sham acupuncture (controls) for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Serum PAB was measured at baseline, and 6 and 12 weeks later. Results We found that serum PAB values decreased significantly in the group receiving the authentic acupuncture compared to the sham treatment (p<0.001) at week 6, and whilst serum PAB increased significantly (p<0.05) in the second phase of the study, a significant difference between two groups remained at 12 weeks (p<0.05). Conclusions Electro-acupuncture in combination with a low-calorie diet was more effective at reducing serum PAB values in obese subjects compared to diet alone. Further work is required to determine the mechanism by which electro-acupuncture has this effect.

Dietary intake of patients with angiographically defined coronary artery disease and that of healthy controls in Iran.

OBJECTIVE: The aim of this study was to investigate the relationship between dietary intake and biomarkers of cardiovascular risk in individuals with and without angiographically defined coronary artery disease. SUBJECTS/METHODS: Coronary angiography was undertaken in 445 individuals who were divided into those with significant disease (>50% occlusion) (Angio+ (n=273)) and those with <50% coronary artery occlusion (Angio- (n=172)). Apparently healthy, non-symptomatic individuals (n=443) were considered as the control group. Dietary intake was assessed using a 24-h dietary recall method and dietary analysis was performed using Diet Plan 6 software. RESULTS: Concentrations of starch, saturated fatty acids, polyunsaturated fatty acids, magnesium, iron and copper in the control group were less than those in the other groups (P<0.05), but after adjusting for total energy intake these differences were no longer apparent. The mean intake of protein, cholesterol, phosphorus, zinc, zinc/copper ratio, selenium, iodine, carotene, vitamin E, niacin, pantothene and pyridoxine was less in the control group compared with the other two groups (P<0.05), and the mean of sugar, fiber, transfatty acids, manganese, folate and vitamin C was higher in the control group than in other groups (P<0.05). Lipid profile values between the three groups did not differ significantly. CONCLUSIONS: These results indicate that the amount of intake of various nutrients can be considered as an independent risk factor for CAD. Further research on the relationship between CAD and nutrient intake, especially intake of essential micronutrients, is needed.

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Determinants of serum copper, zinc and selenium in healthy subjects.

BACKGROUND: We have investigated the association between serum copper, zinc and selenium concentrations, dietary intake, and demographic characteristics, including individual coronary risk factors, in healthy subjects. METHODS: Serum copper, zinc and selenium were measured by atomic absorption spectrometry in 189 healthy subjects. Serum glutathione peroxidase and caeruloplasmin were also determined for each subject. A previously validated food frequency questionnaire was used to estimate the dietary trace element intake. RESULTS: Male subjects had significantly lower serum copper (P<0.001) and caeruloplasmin (P<0.001), and higher serum zinc (P<0.05) and zinc:copper ratio (P<0.001) than female subjects. Significant differences were observed in serum copper and caeruloplasmin concentrations (P<0.01) with age. Weak but significant associations between dietary trace elements and their serum concentrations were observed for zinc (r=0.18, P=0.02), copper (r=0.17, P=0.03) and selenium (r=0.19, P=0.02). Obese subjects had significantly lower serum concentrations of zinc (P<0.05). In multifactorial analysis, dietary zinc (P<0.05), serum high-density lipoprotein-cholesterol (HDL-C) (P<0.05), diastolic blood pressure (P<0.05) and age (P=0.05) emerged as major predictors of serum zinc concentrations. The corresponding predictors for serum copper were C-reactive protein (CRP) (P<0.001), serum HDL-C (P<0.001), gender (P=0.01), physical activity levels (P<0.05) and dietary copper (P<0.05). Serum selenium concentrations were predicted by serum total cholesterol (P<0.01), serum CRP concentrations (P<0.05) and dietary selenium (P<0.03). CONCLUSION: Serum copper, zinc and selenium concentrations are influenced by physiological conditions such as age, diet and gender. Their serum concentrations are also associated with coronary risk factors, including body mass index, levels of physical activity, serum HDL-C and CRP.

What does the lipoprotein oxidation phenomenon mean?

The evidence that oxidative lipid modification may be involved in the genesis of common diseases, such as atherosclerosis, is persuasive, but it was, until recently, conjecture based on in vitro findings, or investigation using experimental animal models. Recent clinical intervention studies in patients at high risk of cardiovascular events have been, at best, inconclusive. This has led to a general consensus that antioxidant supplements are of no value in the prevention of cardiovascular disease in subjects at high risk. However, epidemiological studies have demonstrated that the protective effects of antioxidant supplements, specifically vitamin E, were particularly evident amongst healthy subjects taking supplements. The picture is further clouded by the uncertain mechanism of lipoprotein modification within the artery wall, the possibility that some antioxidants may, under certain conditions, become pro-oxidants, the complex interactions between lipid- and water-soluble antioxidants, and the fact that free-radical-mediated events may only be important in the early stages of atherogenesis. Recent results also suggest that the biological efficacy of antioxidants, such as alpha-tocopherol, may be compromised by the conditions extant within the plaque. It is evidently important that the position on the benefits of antioxidants, whether in food or as supplements, in disease prevention is clarified.

Aluminium administration is associated with enhanced hepatic oxidant stress that may be offset by dietary vitamin E in the rat.

It has been proposed that aluminium toxicity may be mediated, at least in part, by free radical generation. We have investigated the effects of aluminium lactate administration on indices of hepatic oxidant stress, and the consequences of concomitant dietary vitamin E, in male albino Wistar rats. Aluminium lactate was administered for 4 weeks, by ip injection at 10 mg aluminium/kg body weight. Groups of animals received a chow diet containing 0, 5, 15, or 20 mg vitamin E/g of food. A control group of rats received a normal chow diet, without being injected with aluminium. The rats were killed after 4 weeks, and blood and liver tissue removed for the measurement of aluminium and markers of oxidative stress. Plasma and liver aluminium levels were increased in all groups of animals receiving aluminium lactate (P < 0.01), although these levels were significantly reduced in rats receiving concomitant vitamin E (P < 0.05). Aluminium treatment was associated with significantly increased levels of hepatic reactive oxygen species (ROS) (P < 0.01) that were attenuated by concomitant vitamin E (P < 0.05). Hepatic catalase and reduced glutathione levels were both reduced in animals treated with aluminium (P < 0.05).

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25-1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 +/- 0.78 vs. 1.33 +/- 0.46 microg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 +/- 21 IU/mg tissue) compared to the other groups (187 +/- 21; 239 +/- 53; 201 +/- 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 +/- 5.5%) and a deficient diet (0 mg/day) (63.1 +/- 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 +/- 6.3 and 42.8 +/- 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population.

Effect of vitamin E supplementation on circulating cell adhesion molecules pre- and post-coronary angioplasty.

The soluble adhesion molecules P-selectin (sP-selectin) and intercellular adhesion molecule-1 (sICAM-1) are derived from platelets and endothelial cells. Circulating concentrations of these soluble adhesion molecules are raised in patients with atherosclerosis and following percutaneous transluminal coronary angioplasty (PTCA). We have investigated the effects of vitamin E supplements (800 IU/day) on circulating plasma ICAM-1 and P-selectin levels pre- and post-PTCA. Patients, randomized to group, were pre-treated with vitamin E or placebo (soybean oil) for 1 month before routine PTCA. Plasma sICAM-1 and sP-selectin were measured by enzyme-linked immunosorbent assay on blood taken immediately pre- and post-PTCA. Total protein and alpha-tocopherol were measured on the same samples. Plasma alpha-tocopherol concentrations increased in patients receiving vitamin E: 19.1 (1.5) [mean (standard error of the mean, SEM)] mg/mL post-PTCA versus 13.9 (0.6) mg/mL pre-PTCA (n=23; P<0.01). Plasma sP-selectin and sICAM-1 levels were not significantly increased following PTCA in the vitamin E group. Pre-angioplasty mean (SEM) plasma sP-selectin concentration in the vitamin E group was 8.83 (0.97) ng/mg protein; the corresponding mean post-angioplasty value was 9.34 (0.89) ng/mg protein (P=0.85). The mean (SEM) pre-angioplasty sICAM-1 concentration in this group was 2.18 (0.24) ng/mg protein, and was 2.20 (0.23) ng/mg protein following angioplasty (P = 0.84). In the placebo group (n = 24) there was a significant increase in mean (SEM) sP-selectin concentration following angioplasty, from 7.48 (0.73) to 9.70 (0.78) ng/mg protein (P<0.05). The change (mean, SEM) in plasma sP-selectin concentration following angioplasty was significantly greater for the placebo group [2.22 (0.50) ng/mg protein] than for the group receiving vitamin E [0.50 (0.50) ng/mg protein] (P<0.02). This difference remained significant (P<0.05) even after adjustment for pre-angioplasty P-selectin concentrations. Mean (SEM) plasma sICAM-1 concentrations remained unchanged following angioplasty [pre-angioplasty: 2.16 (0.20) ng/mg protein; post-angioplasty: 1.97 (0.13) ng/mg protein]. Vitamin E may therefore limit platelet or endothelial activation during PTCA.

Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons.

OBJECTIVES: To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids. DESIGN: A 6-month double-blind randomized placebo-controlled cross-over study with a 1 -week washout between cross-over periods. METHODS: Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion. Clinic and 24-h ambulatory blood pressure, plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase. RESULTS: Clinic blood pressure did not change between placebo and vitamin C phases. Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure (2.0 +/- 5.2 mmHg; 95% confidence interval 0-3.9 mmHg) but not in diastolic blood pressure. Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased. Regression analysis of the change in high-density lipoprotein (HDL) cholesterol showed a significant effect of sex on the change in HDL cholesterol. In women, but not men, HDL cholesterol increased significantly by 0.08 +/- 0.11 mmol/l, P=0.007. There was no change in low-density lipoprotein cholesterol between treatment periods. CONCLUSION: In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure, which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke.

Dietary copper supplementation reduces atherosclerosis in the cholesterol-fed rabbit.

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. In the present study we have attempted to address this issue directly by investigating the effects of dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Age matched rabbits (n = 16) were fed a 0.25-1% cholesterol diet to maintain plasma cholesterol concentrations at approximately 30 mmol/l. Eight of these animals also received 0.2% copper acetate. Control animals (n = 8) received rabbit chow without supplements. After 13 weeks on the experimental diets the animals were killed. Integrated cholesterol levels were similar for the cholesterol-fed animals (31.1+/-2.5 vs. 29.9+/-1.9 mmol/l weeks; P>0.05). Although integrated plasma copper levels were higher in the animals receiving the copper supplements, these did not differ significantly (19.0+/-4.8 vs. 15.1+/-2.9 micromol/l weeks; P>0.05). Tissue concentrations of copper were higher in the copper fed animals compared to those on cholesterol alone in aortic 14.0+/-0.75 vs. 1.8+/-0.2 microg/g wet tissue; P<0.05), carotid artery (11.4+/-3.5 vs. 4.9+/-0.9 microg/g wet tissue; P<0.05), and hepatic (332.5+/-28.6 vs. 3.3+/-1.1 microg/g wet tissue; P<0.0001) samples. The concentration of copper within the carotid artery was also significantly higher than that within the aorta (7.5+/-1.8 vs. 2.4+/-0.4 microg/g wet tissue; P<0.05). In animals fed a normal rabbit chow aortic, carotid and hepatic copper concentrations were 3.7+/-0.8, 9.4+/-3.4, and 5.0+/-1.6 microg/g, respectively. These values did not differ significantly from the cholesterol-fed animals (P>0.05). Plasma concentrations of caeruloplasmin, the major copper carrying protein, were estimated as plasma ferroxidase activity and were similar for the groups (P>0.05), as were aortic superoxide dismutase activity levels (P>0.05). Copper supplementation was associated with increased mononuclear cell adhesion to the endothelium of the carotid endothelium, with 2.6+/-0.3 adherent monocytes/1000 endothelial cells in the cholesterol plus copper-fed animals compared to 1.3+/-0.3 in the cholesterol-fed group (P = 0.0006), and 0.1+/-0.1 in the control animals (P<0.002). This may reflect the higher concentrations of copper found within the carotid artery. Histology of the thoracic aorta at the level of the third and sixth intercostal arteries, showed that copper supplementation was associated with significantly smaller intimal lesions (P<0.05 and P<0.01, respectively). These data suggest that copper supplements possibly inhibit the progression of atherogenesis.

Dietary vitamin E supplementation inhibits thrombin-induced platelet aggregation, but not monocyte adhesiveness, in patients with hypercholesterolaemia.

Several recent studies have indicated the possible beneficial effects of antioxidants, specifically vitamin E, in primary and secondary coronary prevention. These studies suggest that a diet enriched in vitamin E is insufficient to have a significant protective effect, whereas supplements, in excess of 200 international units (IU) per day, are efficacious in preventing coronary disease in both men and women. The mechanisms by which vitamin E may exert its protection are uncertain, but, vitamin E is lipophilic and has been shown to inhibit the oxidative modification of low density lipoprotein (LDL), a process thought to be of crucial importance in atherogenesis. We have also previously shown that alpha-tocopherol (the biologically most potent isomer of vitamin E) has important direct effects on vascular endothelial and smooth muscle cells. In the present study we have investigated the effects of oral supplements of vitamin E (400 IU per day) on platelet and mononuclear cell function in patients with hypercholesterolaemia. We found that although vitamin E supplementation had no significant effect on mononuclear cell adhesion ex vivo, it had a significant effect on the thrombin-induced platelet aggregation (P < 0.01; ANOVA): 6 weeks after starting the vitamin E supplements, the mean EC50 for thrombin-induced aggregation increased 132% (P < 0.05; paired t-test) compared to treatment with placebo. The effects of vitamin E on platelet function may, in part, explain its anti-atherogenic properties.

Tissue distribution of alpha-tocopherol following dietary supplementation in the rat: effects of concomitant cholesterol feeding.

Vitamin E is a potent, naturally occurring, lipid-soluble antioxidant, which is reported to be protective against several disease processes, including coronary atherosclerosis. We have measured the alpha-tocopherol content of the aorta, liver, skeletal muscle, and kidney of rats fed one of the following diets for 10 weeks: a normal control chow diet (i); or the same diet containing 1% cholesterol (ii); 0.5% vitamin E (iii); or 1% cholesterol plus 0.5% vitamin E (iv). The alpha-tocopherol content of serum and tissue extracts was measured by HPLC using gamma-tocopherol as an internal standard. Tissue and serum cholesterol content was measured using a cholesterol oxidase enzyme reagent kit. In all animals receiving the 1% cholesterol diet, serum cholesterol levels increased significantly (P < 0.005). By the 10th week, mean serum alpha-tocopherol levels rose significantly in both groups of animals receiving dietary vitamin E supplements (P < 0.0001) compared with their respective control group. This was accompanied by a significant increase in the absolute alpha-tocopherol content of liver (8- to 9-fold) and aorta (3- to 4-fold). The alpha-tocopherol content of renal and skeletal muscle tissue was raised 1- to 2-fold in both groups of rats on vitamin E supplements, however the increased attained significance only for the renal tissue. The aortic tissue alpha-tocopherol/cholesterol ratio was 4-fold higher in the rats receiving concomitant 1% cholesterol plus 0.5% vitamin E compared with animals receiving 1% cholesterol alone (P < 0.02), and was 5-fold higher in the rats receiving 0.5% vitamin E compared with those receiving control chow (P < 0.01). These data suggest that dietary vitamin E supplementation results in a differential uptake of alpha-tocopherol, which may be dependent, in part, on selective lipoprotein particle accumulation.

Vitamin E restores endothelium dependent vasodilatation in cholesterol fed rabbits: in vivo measurements by photoplethysmography.

OBJECTIVE: Pulse curve plethysmography was used to examine the effect of vitamin E on endothelium dependent and independent vasodilatation in unanaesthetised cholesterol fed rabbits in vivo. The height of the dicrotic notch was used as an index of general arterial vasodilatation. METHODS: Twenty eight rabbits were divided into three study groups; a control group (group 1, n = 8), a group fed 1% cholesterol (group 2, n = 10), and a group fed 1% cholesterol with the addition of 0.2% vitamin E after four weeks (group 3, n = 10). After six weeks on diet the vasodilator responses to acetylcholine and glyceryl trinitrate were measured by photoplethysmography of the rabbit ear. Recordings were made during light sedation at baseline and during infusion of acetylcholine (1.5, 3.0, 6.0, and 12 micrograms.min-1) and glyceryl trinitrate (3.75, 7.5, and 15.0 micrograms.min-1). In a second set of experiments with control fed rabbits (n = 5), acetylcholine infusions were given before and after infusion of L-nitro-arginine (15 mg). RESULTS: The relative height of the dicrotic notch (which predominantly indicates arterial tone in the larger vessels) was reduced by acetylcholine in a dose dependent manner, but in cholesterol fed rabbits (group 2) this response was significantly decreased. Rabbits receiving concomitant dietary vitamin E responded in a similar manner to controls. The difference was most prominent using acetylcholine at a dose of 3.0 micrograms.min-1, where the mean change from baseline was 11(SEM 4)% in group 2, compared to 31(6)% in group 1 (p = 0.01), and to 26(5)% in group 3 (p = 0.02). Similar differences between the groups were observed for the increase in heart rate during acetylcholine infusions. In contrast, the responses to glyceryl trinitrate were similar in all groups. After infusions of L-nitro-arginine, the responses to acetylcholine were blunted. CONCLUSIONS: Supplementation with vitamin E restored the otherwise reduced vascular response to acetylcholine in cholesterol fed rabbits. Analysis of photoplethysmographic pulse curves is a simple non-invasive method of evaluating arterial vasodilator effects. However, the nature of the measured dilator response needs to be characterised further.