Associations between hypertriglyceridemia, dietary fat intake, oxidative stress, and endothelial activation in men

OBJECTIVE: We examined the associations between intake of different types of dietary fat and plasma levels of oxidative stress and endothelial activation markers in men. METHODS: For that purpose, a complete physical and metabolic profile was assessed. Dietary habits of subjects were determined with a 3-d food record. We also measured fasting plasma 8-iso-prostaglandin F2alpha and oxidized low-density lipoprotein concentrations and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and E-selectin. All these measurements were performed with commercial enzyme-linked immunosorbent assay kits and standards. RESULTS: We found that a high total dietary fat intake was associated with high plasma sICAM-1 (r = 0.40, P < 0.005), sVCAM-1 (r = 0.31, P < 0.05), and E-selectin (r = 0.28, P < 0.05) levels. We also found that in men matched for plasma triacylglycerol levels, those consuming a diet rich in total fat (>105 g/d, n = 21) were characterized by higher circulating levels of sICAM-1 (P < 0.05) and E-selectin (P < 0.05) compared with triacylglycerol-matched individuals with a low total dietary fat intake (<105 g/d, n = 21). However, no significant difference was noted in plasma oxidized low-density lipoprotein levels between groups. Further, we conducted multivariate analyses and found that saturated fatty acid intake was the only dietary variable after inclusion of other dietary variables that contributed to circulating sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.05). CONCLUSION: Our study suggests that high dietary fat consumption is associated with endothelial activation in men and that this detrimental effect is likely attributable to the saturated fatty acid content of the diet.     

Associations of dietary and serum copper with inflammation, oxidative stress, and metabolic variables in adults

There are conflicting data on the associations between copper and glycemia, plasma lipids, and atherosclerotic diseases. Copper has both pro-oxidant and antioxidant effects. We performed a cross-sectional analysis to investigate the associations between dietary copper intake and metabolic variables and serum high-sensitivity C-reactive protein (hs-CRP) in asymptomatic subjects from a population-based cohort (n = 1197) and between serum copper concentration and markers of oxidative stress, including plasma nitrotyrosine (NT) and total antioxidant status (TAS), hs-CRP, and metabolic variables in a subgroup of men from this cohort (n = 231). In all subjects, diastolic blood pressure and circulating glucose, uric acid, and total and LDL-cholesterol concentrations significantly decreased, whereas the hs-CRP concentration increased, from the lowest to the highest tertile of copper intake. In the male subgroup, glucose and total and LDL-cholesterol and TAS decreased, whereas hs-CRP and NT concentrations increased from the lowest to the highest tertile of serum copper concentration. In multiple regression models, dietary copper intake was inversely associated with diastolic blood pressure (P = 0.002), fasting glucose (P < 0.001), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), and uric acid (P < 0.001) and was directly associated with the hs-CRP concentration (P < 0.001). Serum copper concentrations were inversely associated with glucose (P < 0.001), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), and TAS (P < 0.001) and were directly associated with hs-CRP (P < 0.001) and NT concentrations (P < 0.001). Marginal copper deficiency is associated with an unfavorable metabolic pattern, but copper supplementation might not be recommended in view of its association with inflammation and markers of oxidative stress.     

Influence of lycopene and vitamin C from tomato juice on biomarkers of oxidative stress and inflammation

A human study was carried out to investigate whether tomato juice, rich in natural lycopene and fortified with vitamin C, is able to reduce several biomarkers of oxidative stress and inflammation and whether the effect can be attributed to lycopene, vitamin C or any other micronutrient. Following a 2-week depletion phase, volunteers were assigned randomly to ingest either tomato juice with (LC) or without (L) vitamin C fortification for 2 weeks (daily dose 20.6 mg lycopene and 45.5/435 mg vitamin C). Plasma and urine were analysed for carotenoids and vitamin C, lipid status, antioxidant capacity, thiobarbituric acid reactive substances (TBARS) and 8-epi-PGF2alpha, protein carbonyls, cytokines IL-1beta and TNFalpha and C-reactive protein (CRP). The consumption of tomato juice led to a reduction in total cholesterol levels (L: 157.6 v. 153.2 mg/dl, P = 0.008; LC: 153.4 v. 147.4 mg/dl, P = 0.002) and that of CRP (L: 315.6 v. 262.3 microg/l, P = 0.017; LC: 319.2 v. 247.1 microg/l, P = 0.001) in both groups. The vitamin C-fortified juice slightly raised the antioxidant capacity in urine and decreased TBARS in plasma and urine. All other markers were affected to a lesser extent or remained unchanged. Cholesterol reduction was correlated with lycopene uptake (P = 0.003), whereas the other effects could not be related with particular micronutrients. Any beneficial effects of tomato consumption for human health cannot be attributed only to lycopene and, as the additional supplementation with ascorbic acid indicates, a variety of antioxidants might be needed to optimize protection against chronic diseases.     

Evaluation of dietary factors in relation to the biomarkers of oxidative stress and inflammation in breast cancer risk

Objective

This study was conducted to evaluate blood concentrations of inflammatory cytokines and oxidative stress-related biomarkers as risk factors of breast cancer and to determine the relation between these markers and antioxidant nutrient intake.

Methods

Study subjects were 134 patients with breast cancer and 149 controls. Total antioxidant capacity and concentrations of 8-isoprostane, 8-hydroxy-2′-deoxyguanosine, interleukin (IL)-1β, IL-6, and IL-8 of blood samples were determined. A food-frequency questionnaire was used to assess nutrient intake.

Results

Patients with breast cancer had significantly higher blood levels of oxidative stress markers compared with control subjects. Plasma concentrations of IL-1β and IL-6 were significantly higher in patients with breast cancer compared with those of control subjects. In the pooled analysis, total antioxidant capacity was significantly decreased with increasing quartiles of carbohydrate intake but was increased with increasing quartiles of total vitamin A intake and vitamin C intake. In addition, 8-hydroxy-2′-deoxyguanosine concentration was decreased with increasing quartiles of vitamin A and β-carotene. No significant association was found between nutrient intake and cytokine concentrations.

Conclusions

These results suggest that oxidative stress and inflammation may be associated with the risk of breast cancer. Total vitamin A intake was negatively related to oxidative stresses, possibly modifying the risk of breast cancer.     

Nutritional, dietary and postprandial oxidative stress

Nutritional, or dietary oxidative stress denotes a disturbance of the redox state resulting from excess oxidative load or from inadequate nutrient supply favoring prooxidant reactions. Low intake or impaired availability of dietary antioxidants including vitamins E and C, carotenoids, polyphenols, and other micronutrients (e.g., selenium) weakens the antioxidant network. Postprandial oxidative stress, as a subform of nutritional oxidative stress, ensues from sustained postprandial hyperlipidemia and/or hyperglycemia and is associated with a higher risk for atherosclerosis, diabetes, and obesity. In Western societies, a significant part of the day is spent in the postprandial state. Unsaturated fatty acids incorporated into LDL and oxidized LDL are an atherogenic factor. Lipid hydroperoxides present in the diet are absorbed, contributing to the prooxidant load. In hyperlipidemic and hyperglycemic subjects, endothelium-dependent vasodilation is impaired in the postprandial state, making postprandial oxidative stress an important factor modulating cardiovascular risk. Postprandial oxidative stress is attenuated when dietary antioxidants are supplied together with a meal rich in oxidized or oxidizable lipids. Ingestion of dietary polyphenols, e.g., from wine, cocoa, or tea, improves endothelial dysfunction and lowers the susceptibility of LDL lipids to oxidation. Polyphenols affect endothelial function not solely as antioxidants but also as modulatory signaling molecules.     

Effects of curcumin on retinal oxidative stress and inflammation in diabetes

Background

Age-related macular degeneration (AMD) is a disease with multiple risk factors, many of which appear to involve oxidative stress. Macular pigment, with its antioxidant and light-screening properties, is thought to be protective against AMD. A result has been the appearance of dietary supplements containing the macular carotenoids, lutein and zeaxanthin. More recently, a supplement has been marketed containing, in addition, the third major carotenoid of the macular pigment, meso-zeaxanthin. The purpose of the study was to determine the effectiveness of such a supplement in raising macular pigment density in human subjects.

Methods

A 120 day supplementation study was conducted in which 10 subjects were given gel-caps that provided 20 mg/day of predominantly meso-zeaxanthin, with smaller amounts of lutein and zeaxanthin. A second group of 9 subjects were given gel caps containing a placebo for the same 120 day period. Prior to and during the supplementation period, blood serum samples were analyzed by high performance liquid chromatography for carotenoid content. Similarly, macular pigment optical density was measured by heterochromatic flicker photometry. Differences in response between the supplementation and placebo groups were tested for significance using a student's t-test.

Results

During supplementation with the carotenoids, blood samples revealed the presence of all three carotenoids. Macular pigment optical density, measured at 460 nm, rose at an average rate of 0.59 ± 0.79 milli-absorbance unit/day in the 10 supplemented subjects. This was significantly different from the placebo group (9 subjects) for whom the average rate was -0.17 ± 0.42 milli-absorbance units/day.

Conclusion

We have shown for the first time that meso-zeaxanthin is absorbed into the serum following ingestion. The data indicate that a supplement containing predominantly meso-zeaxanthin is generally effective at raising macular pigment density, and may turn out to be a useful addition to the defenses against AMD.     

A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men

There is a demand and need for healthy solid dietary fats. However, synthetic fats can be tailored to contain specific physiologic properties. Our goal was to design dietary solid test fats that would be both beneficial to the atherogenic lipid profile and stable against lipid peroxidation. Sixteen men (age 35-75 y) substituted 80 g of their normal dietary fat intake with test fat for two periods of 21 d each in a double-blind, randomized, crossover study. Although solid, both test fats were low in cholesterol-raising SFA. Test fat "F" contained 5 g/100 g long chain (n-3) fatty acids matched by oleic acid in test fat "O." Plasma total triacylglycerol (TAG), VLDL TAG, cholesterol in VLDL, and intermediate density lipoproteins (IDL) were lower (P < 0.05), whereas apolipoprotein (apo) B of the large LDL-2 (d = 1031-1042 g/L) subclass, and cholesterol of HDL(2b) subclass, were higher after intake of F than O fat (P < 0.05). There was no difference in the effect on in vivo oxidation measured as the ratio of plasma isoprostanes F(2) to arachidonic acid and urinary isoprostanes, whereas the vitamin E activity/plasma total lipids ratio was higher after intake of F than O (P = 0.008). In conclusion, a solid dietary fat containing (n-3) PUFA decreased plasma TAG, VLDL, and IDL cholesterol, and redistributed lipoprotein subclasses in LDL and HDL, with a higher concentration of the larger and less atherogenic subfractions. These changes took place without an increase in oxidative stress as measured by in vivo markers.     

Influence of dietary conjugated linoleic Acid and fat source on body fat and apoptosis in mice

OBJECTIVE: To determine whether altered dietary essential fatty acid (linoleic and arachidonic acid) concentrations alter sensitivity to conjugated linoleic acid (CLA)-induced body fat loss or DNA fragmentation. RESEARCH METHODS AND PROCEDURES: Mice were fed diets containing soy oil (control), coconut oil [essential fatty acid deficient (EFAD)], or fish oil (FO) for 42 days, and then diets were supplemented with a mixture of CLA isomers (0.5% of the diet) for 14 days. Body fat index, fat pad and liver weights, DNA fragmentation in adipose tissue, and fatty acid profiles of adipose tissue were determined. RESULTS: The EFAD diet decreased (p < 0.05) linoleic and arachidonic acid in mouse adipose tissue but did not affect body fat. Dietary CLA caused a reduction (p < 0.05) in body fat. Mice fed the EFAD diet and then supplemented with CLA exhibited a greater reduction (p < 0.001) in body fat (20.21% vs. 6.94% in EFAD and EFAD + CLA-fed mice, respectively) compared with mice fed soy oil. Dietary FO decreased linoleic acid and increased arachidonic acid in mouse adipose tissue. Mice fed FO or CLA were leaner (p < 0.05) than control mice. FO + CLA-fed mice did not differ in body fat compared with FO-fed mice. Adipose tissue apoptosis was increased (p < 0.001) in CLA-supplemented mice and was not affected by fat source. DISCUSSION: Reductions in linoleic acid concentration made mice more sensitive to CLA-induced body fat loss only when arachidonic acid concentrations were also reduced. Dietary essential fatty acids did not affect CLA-induced DNA fragmentation.     

Augmentation of superoxide generation in phagocytosing murine peritoneal macrophages by dietary restriction

The effects of dietary restriction on the generation of superoxide anion (O2-) in phagocytosing mouse peritoneal macrophages (MPs) were investigated. MPs obtained from diet-restricted mice generated larger amount of O2- during phagocytosis of opsonized zymosan than those from unrestricted mice. This augmentation of the O2- generation was not inhibited by the protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). However, the augmentation was clearly disappeared when the calmodulin (CaM) antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) was added. These results strongly suggest that the augmentation of O2- generation in phagocytosing MPs by dietary restriction is due to the increased activity of CaM in the MPs, and that PKC is not involved in the augmentation. It is thought that one of the major factors for the reduced incidence of tumor and infection in diet-restricted animals is the augmentation of O2- generation in MPs.     

Lowering dietary saturated fat and total fat reduces the oxidative susceptibility of LDL in healthy men and women

The present study examined the effects of reducing dietary total fat and saturated fat (SFA) on LDL oxidative susceptibility in 27 healthy men and women (age 24-65 y). Each subject consumed each of three diets for 8 wk: an average American diet (AAD, 34% energy from fat, 15% from SFA), a Step-1 diet (29% fat, 9% SFA) and a very low SFA diet (Low-Sat, 25% fat, 6% SFA). In vitro LDL oxidation was assessed by copper-mediated oxidation, as measured by the kinetics of conjugated diene formation and lipid peroxide formation. Compared with the AAD, plasma LDL-cholesterol (LDL-C) and HDL cholesterol levels were 8% lower (P: = 0.16 and P: = 0.11, respectively), in subjects when they consumed the Step-1 diet and 11% (P: < 0.03) and 14% (P: < 0.057) lower, respectively, when they consumed the Low-Sat diet. Conjugated diene production and oxidation rate were 7% (P: < 0. 05) and 9% (P: < 0.05) lower, respectively. The reduction of lipid peroxide formation was 9% (P: < 0.05) in subjects when they consumed the Low-Sat diet vs. the AAD. In addition, lipid peroxide and conjugated diene formation were positively correlated with plasma total and LDL-C and apolipoprotein B (apo B) levels (r = 0.5-0.6, P: < 0.001), suggesting that quantity of LDL is an important determinant of oxidative modification. Furthermore, at the same level of apo B or LDL-C, LDL from subjects when they consumed either Step-1 or Low-Sat diets was less susceptible (P: < 0.05) to oxidation than those when they consumed the AAD, suggesting that qualitative changes also affect LDL oxidative susceptibility. Therefore, the benefits of lowering dietary SFA may extend beyond decreasing LDL-C levels and include favorable qualitative changes in LDL that further decrease risk of coronary heart disease.     

Effect of varying dietary fat levels on rat growth and oxidative DNA damage.

Dietary fat has previously been shown to have somewhat complicated relationships to levels of oxidative stress in rats. In this study, we examined the effects of five different dietary fat intakes on levels of oxidative DNA damage in rats. Animals fed diets containing 3%, 5%, 10%, or 15% corn oil had body weights that were similar after 20 weeks. Animals fed a 20% fat diet, however, had significantly higher mean body weight than any other group. Levels of 5-hydroxymethyl-2'-deoxyuridine, one marker of oxidative DNA damage, had different relationships to dietary fat in blood and mammary gland. In blood, levels increased with dietary fat levels, and the highest levels were observed with the 20% fat diet (65% higher levels than with the 3% fat diet). In mammary gland, a plateau-type effect was observed, with maximal levels of oxidative DNA damage being obtained using 10% fat (representing a 68% increase relative to the 3% fat diet). This could be a result of induction of compensatory mechanisms in response to a high-fat diet in mammary gland but not in the short-lived nucleated blood cells. Oxidative DNA damage levels in blood thus appear to be a marker of dietary fat intake. In mammary gland, however, levels of DNA damage are consistent with previously observed promotional effects of dietary fat on mammary gland tumorigenesis at lower levels of fat intake with little or no incremental promoting effects at higher levels of fat intake.     

Lack of an influence of dietary fat on murine natural killer cell activity

The influence of the degree of saturation and the concentration of dietary fat on murine natural killer (NK) cell activity was investigated using C3H/HeN and C57BL/6N mice. Mice were fed purified diets containing either 0% fat (fat free), 5 or 20% safflower oil or 5 or 20% palm oil. Safflower oil and palm oil were used because they are comparable in carbon chain length but vary in the amount of linoleic acid [18:2(n-6)]. Cytotoxicity of splenic NK cells from mice stimulated or unstimulated by the interferon inducer poly I:C was measured against either the YAC-1 lymphoma or line 168 mammary tumor targets. The number of asialo GM1+ cells was not influenced by concentration or degree of saturation of dietary fat. Generally, dietary fat had no consistent influence on NK cell cytotoxicity of spleen cells from either the high responder C3H/HeN mice or the moderate responder C57BL/6N mice against either tumor target. The level of 18:2(n-6) in NK cell-enriched splenic lymphocytes increased with greater levels of dietary safflower oil. Nevertheless, there appeared to be no correlation between lymphocyte fatty acid composition and NK cell cytotoxic capabilities. Therefore, the concentration of dietary safflower or palm oil, and thus 18:2 (n-6), did not appear to effect the number or activity of murine NK cells.     

Influence of early weaning and dietary fat on immune responses in adult rats

Equal numbers of female rats, either prematurely weaned at 14 days of age or allowed to nurse for 21 days, were pair-fed a diet containing either vegetable oil or cholesterol-enriched animal fat for 95 days. Thereafter all animals received the animal fat diet until 11 months of age. Rats were then immunized with sheep erythrocytes and the antibody response quantified. There was no significant effect of early weaning or diet on the number of plaque-forming splenocytes or on serum hemolysins. A significant positive correlation between HDL cholesterol and both plaque-forming cells and hemolysin titres was detected in the groups fed animal fat. Significant impairment in splenocyte blastogenic response to phytohemagglutinin was observed in rats receiving animal fat prior to 95 days. Separate groups of rats were infected 5 days before death with Listeria monocytogenes. Splenocyte blastogenesis was impaired in the group fed animal fat to a degree similar to that observed in uninfected rats fed the same diet, and there were increased numbers of bacteria recovered from the spleen and kidney of animals whose early diet contained animal fat. We conclude that the fat content of the early postweaning diet has an impact on immune responses which persists into adulthood.     

Mangiferin decreases inflammation and oxidative damage in rat brain after stress

Purpose

Stress exposure elicits neuroinflammation and oxidative damage in brain, and stress-related neurological and neuropsychiatric diseases have been associated with cell damage and death. Mangiferin (MAG) is a polyphenolic compound abundant in the stem bark of Mangifera indica L. with antioxidant and anti-inflammatory properties in different experimental settings. In this study, the capacity of MAG to prevent neuroinflammation and brain oxidative damage induced by stress exposure was investigated.

Methods

Young–adult male Wistar rats immobilized during 6?h were administered by oral gavage with increasing doses of MAG (15, 30, and 60?mg/Kg), respectively, 7?days before stress.

Results

Prior treatment with MAG prevented all of the following stress-induced effects: (1) increase in glucocorticoids (GCs) and interleukin-1β (IL-1β) plasma levels, (2) loss of redox balance and reduction in catalase brain levels, (3) increase in pro-inflammatory mediators, such as tumor necrosis factor alpha TNF-α and its receptor TNF-R1, nuclear factor-kappa B (NF-κB) and synthesis enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), (4) increase in lipid peroxidation.

Conclusions

These multifaceted protective effects suggest that MAG administration could be a new therapeutic strategy in neurological/neuropsychiatric pathologies in which hypothalamic/pituitary/adrenal (HPA) stress axis dysregulation, neuroinflammation, and oxidative damage take place in their pathophysiology.     

Phthalate-induced oxidative stress and association with asthma-related airway inflammation in adolescents

Background

In Belgium, around 8.5% of the children have asthmatic symptoms. Increased asthma risk in children has been reported in relation to exposure to phthalate plasticizers but the underlying mechanisms are largely unknown.

Influence of dietary fat on beta-carotene absorption and bioconversion into vitamin A

Dietary fat facilitates the utilization of carotenoids and, based on serum beta-carotene or retinol responses following ingestion of meals containing carotene and fat sources, it has been reported that the amount of fat required in a meal may be minimal (approximately 3-5 g). However, the dietary fat requirement for optimal carotene utilization in humans cannot be fully ascertained without longer-term dose-response studies that measure the changes in vitamin A body stores in response to varying levels of dietary fat. In humans, vitamin A body stores can be determined by use of stable isotope-dilution methods. Animal studies have shown that although the level of dietary fat has no effect on serum vitamin A concentrations of animals fed beta-carotene, higher liver vitamin A concentrations were found in those that ingested higher fat levels. Other factors that might influence the relationship of fat intake and beta-carotene utilization include the type of fat ingested, physicochemical properties of the carotenoid source, amount of carotene ingested, whether fat and beta-carotene sources are provided in the same meal, the presence of helminthic infections, age, and vitamin A status.