Kinetics of transfer of alpha-tocopherol between model and native plasma lipoproteins

The rate of spontaneous transfer of alpha-tocopherol, cholesterol and beta-carotene between model and native lipoproteins was measured to determine the mechanism and kinetics of equilibration of these lipids in plasma. Cholesterol and alpha-tocopherol transfer from apolipoprotein A-I/1-palmityl-2- oleoylphosphatidylcholine ( POPC ) recombinants to bovine brain ganglioside/ POPC single bilage vesicles with half-times of approximately 20 min and 70 min, respectively. Under identical conditions, there is no significant transfer of beta-carotene even after an 18-h incubation period. alpha-Tocopherol transfers from apolipoprotein A-II/dimyristoylphosphatidylcholine recombinants with a half-time of 40 min and an activation energy of 17.2 kcal/mol. Incubation of high-density lipoproteins containing alpha-[3H]tocopherol with low-density lipoproteins or very-low-density lipoproteins results in the equilibration of the labelled lipid between the lipoprotein classes in 1 h. A comparison of the rates of transfer indicates that alpha-tocopherol equilibrates 2-3-times more slowly than cholesterol but on a time scale much shorter than the lifetime of lipoproteins in the circulation. Thus, the distribution of alpha-tocopherol is not kinetically controlled but determined thermodynamically by the partitioning between the total amount of lipid in each compartment. The spontaneous transfer of beta-carotene is too slow for this equilibration to occur.     

Comparison of exchange of alpha-tocopherol and free cholesterol between rat plasma lipoproteins and erythrocytes.

The simultaneous exchange of (3h)tocopherol and (14C)cholesterol between rat plasma, rat plasma lipoproteins, and RBC was studied in vitro to compare quantitavely (a) the fractional exchange rates and (b) the half-times for isotope equilibration. In all incubations of RBC with plasma or with plasma lipoprotein fractions, (14C)cholesterol approached equilibrium more rapidly than (3H)tocopherol. When the RBC contained the initial radioactivity, the half-times for equilibration with plasma of cholesterol and of tocopherol were 1.0 and 2.2 hr, respectively. However, the fractional exchange rates (KRBC leads to plasma) were 0.097/hr for cholesterol and 0.188/hr for tocopherol, indicating that the RBC tocopherol pool is turning over almost twice as rapidly as the RBC cholesterol pool. The rat plasma lipoproteins were separated into five fractions by successive ultracentrifugation. Only two fractions, the high density lipoproteins (d 1.063-1.21) and the very low density lipoproteins (d is less than 1.006), participated to a significant extent in the exchange of either tocopherol or cholesterol with RBC. Cholesterol exchange between individual rat plasma lipoproteins and RBC had the same half-times for isotope equilibrium for the very low and high density lipoproteins, and the RBC fractional exchange rates were proportional to the amount of cholesterol in the lipoproteins. In tocopherol exchange between individual rat plasma lipoproteins and RBC, the very low density lipoprotein tocopherol did not equilibrate completely with the RBC. However, the initial rate of tocopherol exchange appeared to be the same for very low and high density lipoproteins. The very low density lipoproteins were disrupted by repeated freezing and thawing or by dehydrating and rehydrating, and analysis of the resulting lipoproteins indicated that free cholesterol was associated more closely than tocopherol with the phospholipid-protein portion of the molecule, which is thought to be on the surface. This difference in distribution of tocopherol and free cholesterol within very low density lipoproteins could account for their different rates of exchange and for the nonequilibrium of tocopherol between RBC and very low density lipoproteins.     

Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants.

OBJECTIVES: To determine the extent to which plasma antioxidant concentrations in people with habitual low intake of fruit and vegetables respond to increased intakes of these foods. To examine whether advice to increase fruit and vegetables will result in reduction of concentrations of total and low density lipoprotein cholesterol. DESIGN: Randomised controlled trial in which intervention and control groups were followed up for eight weeks. The intervention group was asked to consume eight servings of fruit and vegetables a day. SETTING: Dunedin, New Zealand. SUBJECTS: Eighty seven subjects with normal lipid concentrations who ate three or fewer servings of fruit and vegetables daily. MAIN OUTCOME MEASURES: Plasma concentrations of vitamin C, retinol, alpha and beta carotene, alpha tocopherol, lipids, and lipoproteins. Dietary intake assessed with diet records over four days. RESULTS: The mean plasma vitamin C, alpha carotene, and beta carotene concentrations increased in parallel with increased dietary intake of fruit and vegetables in the intervention group. Concentrations of retinol, alpha tocopherol, lipids, and lipoproteins remained unchanged despite some increase in dietary vitamin E and a small reduction in saturated fat intake. CONCLUSIONS: Following a recommendation to increase fruit and vegetable consumption produces change in plasma concentrations of vitamin C, alpha carotene, and beta carotene likely to reduce incidence of cancer. More specific dietary advice to modify fat intake may be necessary to reduce the risk of cardiovascular disease mediated by lipoprotein and vitamin E.     

Neutrophil superoxide-anion generating capacity in chronic smoking: Effect of long-term α-tocopherol therapy

We investigated whether long-term alpha-tocopherol therapy in chronic smoking affects superoxide generating capacity of neutrophils ex vivo. To this purpose, we randomly assigned 128 male chronic smokers (37 +/- 21 pack years of smoking) to treatment with placebo (n = 64) or alpha-tocopherol (400 IU dL-a-tocopherol daily, n = 64). After two years of therapy, we measured phorbol 12-myristate 13-acetate-induced superoxide production of isolated neutrophils and of diluted whole blood by monitoring reduction of ferricytochrome c and luminol-enhanced peroxidase-catalyzed chemiluminescence. Plasma lipids and lipoproteins were not different between the two treatment groups. As expected, concentrations of alpha-tocopherol in plasma and in low-density lipoproteins were markedly elevated in the supplemented group compared to the placebo group (+ 120%, P < 0.0001 and + 83%, P < 0.0001, respectively). Consequently, resistance to in vitro oxidation of low-density lipoproteins (reflected by lag time of conjugated diene formation) was higher in the supplemented group than in the placebo group (+ 22%, P < 0.0001). Superoxide generating capacity of neutrophils and superoxide production in diluted whole blood did not differ between alpha-tocopherol and placebo group. It is concluded that in chronic smoking long-term supranormal alpha-tocopherol intake does not reduce neutrophil superoxide-anion generating capacity, despite large increases in the concentrations of alpha-tocopherol in plasma and in low-density lipoproteins.     

Response of Whole Blood,Erythrocyte and Plasma Vitamin E Content to Dietary Vitamin E Intake in the Chick

Whole blood, red blood cells (RBC), and plasma vitamin E (VE) levels in chicks fed dietary VE (dl-α-tocopheryl acetate, dl-αTa) supplementation in steps of 0.0, 5.0, 10.0, 15.0, 20.0 and 30.0 mg/Kg were determined to examine their usefulness as an index of VE status. The increase in VE level was significant and linear in whole blood (r = 0.90), RBC (r = 0.89) and plasma (r = 0.93) in response to dietary VE intake. There was a close correlation between VE in plasma vs whole blood (r = 0.90), plasma vs RBC (r = 0.91) and whole blood vs RBC (r = 0.95). The plasma VE content was 1.2–1.8 times greater than that of whole blood, and 6.6–12.5 times greater than that of RBC. The plasma total lipids content was not affected by the dietary VE intake, whereas the level of VE in the plasma total lipids was significantly increased with increasing supplementation. Alpha tocopherol was the major isomer (ca 92 %) of VE in whole blood, RBC and plasma at hatching. The small proportions of β-tocopherol (ca 2 %), γ-tocopherol (ca 5 %) and α-tocotrienol (ca 1 %) observed at 1 day of age had decreased or totally disappeared by 7 days of age after feeding the VE-free basal diet. The data showed that in the chick, the whole blood and RBC levels of VE were as sensitive and reliable indexes of dietary VE status as was that of the plasma.     

Alpha-tocopherol supplementation does not affect monocyte endothelial adhesion or C-reactive protein levels but reduces soluble vascular adhesion molecule-1 in the plasma of healthy subjects

Vascular monocyte retention in the subintima is pivotal to the development of cardiovascular disease and is facilitated by up-regulation of adhesion molecules on monocytes/endothelial cells during oxidative stress. Epidemiological studies have shown that cardiovascular disease risk is inversely proportional to plasma levels of the dietary micronutrients, vitamin C and vitamin E (alpha-tocopherol). We have tested the hypothesis that alpha-tocopherol supplementation may alter endothelial/monocyte function and interaction in subjects with normal ascorbate levels (> 50 microM), as ascorbate has been shown to regenerate tocopherol from its oxidised tocopheroxyl radical form in vitro. Healthy male subjects received alpha-tocopherol supplements (400 IU RRR-alpha-tocopherol/day for 6 weeks) in a placebo-controlled, double-blind intervention study. There were no significant differences in monocyte CD11b expression, monocyte adhesion to endothelial cells, plasma C-reactive protein or sICAM-1 concentrations post-supplementation. There was no evidence for nuclear translocation of NF-kappaB in isolated resting monocytes, nor any effect of alpha-tocopherol supplementation. However, post-supplementation, sVCAM-1 levels were decreased in all subjects and sE-selectin levels were increased in the vitamin C-replete group only; a weak positive correlation was observed between sE-selectin and alpha-tocopherol concentration. In conclusion, alpha-tocopherol supplementation had little effect on cardiovascular disease risk factors in healthy subjects and the effects of tocopherol were not consistently affected by plasma vitamin C concentration.     

Plasma beta carotene in Alzheimer's disease. Association with cerebrospinal fluid beta-amyloid 1-40, (Abeta40), beta-amyloid 1-42 (Abeta42) and total Tau

We studied the plasma beta carotene concentrations in 40 Alzheimer's disease patients and the association with cerebrospinal fluid beta-amyloid 1-40, (Abeta40), cerebrospinal fluid beta-amyloid 1-42 (Abeta42) and cerebrospinal fluid total Tau. We found that patients with plasma beta carotene levels below the 25th percentile had 55% reduced ratios of Abeta40/Tau and 51% reduced ratios of Abeta 40/Abeta 42 compared with patients in the highest quartile. Mean Tau concentrations in the lowest quartile of plasma beta-carotene levels were 74% higher compared with the highest quartile of plasma beta-carotene levels. Thus, we could demonstrate an statistically significant association between beta carotene levels in plasma and neurochemical markers in the cerebrospinal fluid of Alzheimer's disease patients.     

Oxidative stress in subjects affected by celiac disease

In order to study the role of oxidative stress in celiac disease, protein carbonyl groups, thiobarbituric acid-reactive substance and pentosidine were evaluated in the plasma of nine patients with asymptomatic celiac disease and in a control group (n = 25). Plasma alpha-tocopherol, retinol and lipids were determined in the same samples. The levels of markers of oxidative stress derived from both protein (carbonyl groups) and lipids (thiobarbituric acid-reactive substances) were significantly higher in celiac disease patients, whereas lipoproteins and alpha-tocopherol were significantly lower. These data indicate that in celiac disease, even when asymptomatic, a redox imbalance persists; this is probably caused by an absorption deficiency, even if slight. Dietary supplementation with antioxidant molecules may offer some benefit and deserves further investigation.     

Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-alpha-tocopherol: studies using deuterated tocopherols

The transport and secretion of vitamin E in lipoproteins have been studied in cynomolgus monkeys fed tocopherols labeled with different amounts of deuterium. The animals were fed a single dose of vitamin E containing 60 mumol of each 2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate; alpha-tocopherol with natural stereochemistry), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate; alpha-tocopherol with unnatural stereochemistry), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol; gamma-tocopherol with natural stereochemistry). Chylomicrons, as well as the other plasma lipoproteins, contained equal concentrations of all three tocopherols at the earliest time points after feeding suggesting that all three tocopherols were absorbed equally. At later times plasma lipoproteins became preferentially enriched in d6-RRR-alpha-tocopherol. This is likely to be due to hepatic secretion of VLDL (very low density lipoproteins) and other lipoproteins, which were enriched in d6-RRR-alpha-tocopherol, as demonstrated in the lipoproteins isolated from perfused livers that had been obtained 24 h following the administration of the deuterated tocopherols. Taken together these data demonstrate that the liver, not the intestine, is the likely site of discrimination between tocopherol isomers and that the liver secretes nascent lipoproteins preferentially enriched in d6-RRR-alpha-tocopherol.     

Long-term kinetic study of beta-carotene, using accelerator mass spectrometry in an adult volunteer

We present a sensitive tracer method, suitable for in vivo human research, that uses beta-[(14)C]carotene coupled with accelerator mass spectrometry (AMS) detection. Using this approach, the concentration-time course of a physiological (306 microgram 200 nCi) oral dose of beta-[(14)C]carotene was determined for 209 days in plasma. Analytes included beta-[(14)C]carotene, [(14)C]retinyl esters, [(14)C]retinol, and several [(14)C]retinoic acids. There was a 5.5-h lag between dosing and the appearance of (14)C in plasma. Labeled beta-carotene and [(14)C]retinyl esters rose and displayed several maxima with virtually identical kinetic profiles over the first 24-h period; elevated [(14)C]retinyl ester concentrations were sustained in the plasma compartment for >21 h postdosing. The appearance of [(14)C]retinol in plasma was also delayed 5.5 h postdosing and its concentration rose linearly for 28 h before declining. Cumulative urine and stool were collected for 17 and 10 days, respectively, and 57.4% of the dose was recovered in the stool within 48 h postdosing. The stool was the major excretion route for the absorbed dose. The turnover times (1/k(el)) for beta-carotene and retinol were 58 and 302 days, respectively. Area under the curve analysis of the plasma response curves suggested a molar vitamin A value of 0.53 for beta-carotene, with a minimum of 62% of the absorbed beta-carotene being cleaved to vitamin A.In summary, AMS is an excellent tool for defining the in vivo metabolic behavior of beta-carotene and related compounds at physiological concentrations. Further, our data suggest that retinyl esters derived from beta-carotene may undergo hepatic resecretion with VLDL in a process similar to that observed for beta-carotene.     

Effect of beta-carotene administration on reproductive function of horse and pony mares

The objective of this study was to determine whether supplemental beta-carotene would influence reproductive function in mares maintained on spring and summer pastures and to characterize plasma carotene concentrations during the estrous cycle. Carotene concentrations in plasma did not vary with day of estrous cycle (P = 0.7455). Mares receiving every other day injections of beta-carotene (400 mg; n = 4) or saline (10 ml; n = 4) during proestrus/estrus did not differ in plasma estradiol (E(2)) concentrations (P = 0.6313), follicle development (P = 0.8068), or plasma progesterone (P(4)) concentrations during the following diestrus (P = 0.4954). Moreover, no differences in plasma P(4) concentrations (P = 0.9047) were detected between mares receiving every other day injections of beta-carotene (400 mg; n = 4) or saline (10 ml; n = 4) during diestrus. However, administration of beta-carotene raised plasma carotene concentrations relative to controls when injected during proestrus/estrus (P = 0.0096) and diestrus (P = 0.0099). Pregnancy rates (P = 0.4900) and number of cycles required for pregnancy (P = 0.2880) were similar for mares administered injections of saline (10 ml; n = 37), beta-carotene (400 mg; n = 37), vitamin A (160,000 IU; n = 38), or vitamin A + beta-carotene (160,000 IU + 400 mg; n = 43), on the first or second day of estrus and on the day of breeding. Therefore, these results collectively suggest that supplemental beta-carotene does not affect the reproductive function of mares fed adequate dietary carotene. Whether supplemental beta-carotene would enhance reproductive function in mares on low carotene diets warrants further investigation.     

Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer's disease.

Because increased oxidation is an important feature of Alzheimer's disease (AD) and low concentrations of antioxidant vitamins C and E have been observed in cerebrospinal fluid (CSF) of AD patients, supplementation with these antioxidants might delay the development of AD. Major targets for oxidation in brain are lipids and lipoproteins. We studied whether supplementation with antioxidative vitamins E and C can increase their concentrations not only in plasma but also in CSF, and as a consequence decrease the susceptibility of lipoproteins to in vitro oxidation. Two groups, each consisting of 10 patients with AD, were for 1 month supplemented daily with either a combination of 400 IU vitamin E and 1000 mg vitamin C, or 400 IU vitamin E alone. We found that supplementation with vitamin E and C significantly increased the concentrations of both vitamins in plasma and CSF. Importantly, the abnormally low concentrations of vitamin C were returned to normal level following treatment. As a consequence, susceptibility of CSF and plasma lipoproteins to in vitro oxidation was significantly decreased. In contrast, the supplementation with vitamin E alone significantly increased its CSF and plasma concentrations, but was unable to decrease the lipoprotein oxidizability. These findings document a superiority of a combined vitamin E + C supplementation over a vitamin E supplementation alone in AD and provide a biochemical basis for its use.     

Effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption

This study examined the effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and β‐carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and α‐tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with β‐carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing β‐carotene. The results indicate that β‐carotene supplementation can prevent ethanol‐induced liver damage and increase GSH concentrations in erythrocytes and the liver. Copyright © 2009 John Wiley & Sons, Ltd.     

Antioxidative effects of turmeric, rosemary and capsicum extracts on membrane phospholipid peroxidation and liver lipid metabolism in mice

Phospholipid hydroperoxides (PLOOH) in the plasma, red blood cells (RBC) and liver of mice were measured after dietary supplementation for one week (1% w/w of diet) with a turmeric extract (curcuminoid), hexane extract of rosemary, and supercritical CO2-extracted capsicum pigment (supplemented with alpha-tocopherol to prevent fading). A lower PLOOH level was found in RBC of the spice extract-fed mice (65-74% of the non-supplemented control mice). The liver lipid peroxidizability induced with Fe2+/ascorbic acid was effectively suppressed by dietary supplementation with the turmeric and capsicum extracts to mice. While no difference in the plasma lipids was observed, the liver triacylglycerol concentration of the turmeric extract-fed mice was markedly reduced to one-half of the level in the control mice. These findings suggest that these spice extracts could act antioxidatively in vivo by food supplementation, and that the turmeric extract has the ability to prevent the deposition of triacylglycerols in the liver.     

Stories about acyl chains

The effect of dietary polyunsaturated fatty acids and alpha-tocopherol supplementation on erythrocyte lipid peroxidation and immunocompetent cells in mice was studied comparatively using seven dietary oils (15% oil/diet, w/w) including fish oil rich in eicosapentaenoic acid (EPA, 20:5, n-3) and docosahexaenoic acid (DHA, 22:6, n-3). A 43% increase in spleen weight, about twice as many spleen cells and no change in the subpopulations of spleen cells, as well as a significant depression of mitogen-induced blastogenesis of both T and B cells in the spleen were observed in mice fed fish oil for 30 days in comparison with soybean oil diet-fed mice. In the fish oil diet-fed mice, membranous lipid hydroperoxide (hydroperoxides of phosphatidylcholine and phosphatidylethanolamine) accumulation as a marker of oxidative senescence in red blood cells (RBC) was 2.7-3.5 times higher than that in mice fed soybean oil, although there was no difference in the plasma phosphatidylcholine hydroperoxide concentration. In spite of the supplementation of alpha-tocopherol to up to 10 times the level in the basal diet, the degeneration of spleen cells and the stimulated oxidative senescence of RBC found by the fish oil feeding could not be prevented. The results suggest that oral intake of excess polyunsaturated fatty acids, i.e. EPA and DHA, in a fish oil diet can lead to acceleration of membrane lipid peroxidation resulting in RBC senescence linked to the lowering of immune response of spleen cells, and that supplementation of alpha-tocopherol as antioxidant does not always effectively prevent such oxidative degeneration as observed in spleen cells and RBC in vivo.     

Spectrophotometric method for determination of tocopherol in red blood cells

A relatively rapid procedure is described for the spectrophotometric determination of total tocopherol in red blood cells (RBC) based on a modification of the original Emmerie-Engel reaction. The critical feature in this method is the presence of a large amount of an added antioxidant, pyrogallol or ascorbic acid, during the saponification and extraction stages and the use of thin-layer chromatography for tocopherol purification. The total tocopherol levels of plasma and erythrocytes were determined for a number of human subjects, for patients with abetalipoproteinemia, and for rats. It was found that these levels had a wide range in normal human subjects but that the ratio of RBC to plasma tocopherol was relatively constant and equal to 0.18, uncorrected, and 0.21 when both RBC and plasma values were corrected to 100% recovery. The RBC-to-plasma ratio for rats was 0.39. The accuracy of this ratio determined by the spectrophotometric procedure was verified by measuring the distribution of [(14)C]tocopherol in RBC and plasma when radioactive vitamin E was introduced into the blood by both in vitro and in vivo techniques. The addition of radioactive tocopherol to RBC or plasma at the initial stage of the analysis permits an accurate determination of the total tocopherol in RBC or plasma by calculations based on the recovery of the added isotope. This procedure for erythrocyte tocopherol analysis is compared with a gas-liquid chromatographic method in current use.     

Tocopherol in human platelets.

A spectrophotometric method was used to determine the total tocopherol levels in platelets, plasma, and erythrocytes from human subjects. The platelets contained about three times as much total tocopherol per cell as erythrocytes. This difference was not related to the content of polyunsaturated fatty acids in platelets and erythrocytes. In vitro incubation resulted in significant uptake of tocopherol by plasma and RBC, whereas no uptake was observed into platelets. A 3-month period of tocopherol treatment increased the level of tocopherol in plasma and erythrocytes, whereas the platelet level was unchanged. Tocopherol treatment did not interfere with platelet function or platelet lipid metabolism. The tocopherol fractions of platelets, red cells, and plasma were similar, and alpha-tocopherol was the main fraction.     

Pro-carcinogenic activity of beta-carotene, a putative systemic photoprotectant.

Beta-carotene is a strong singlet oxygen quencher and antioxidant. Epidemiologic studies have implied that an above average intake of the carotenoid might reduce cancer risks. Earlier studies found that the carotenoid, when added to commercial closed-formula rodent diets, provided significant photoprotection against UV-carcinogenesis in mice. Clinical intervention trials found that beta-carotene supplementation evoked no change in incidence of nonmelanoma skin cancer. However, when smokers were supplemented with the carotenoid a significant increase in lung cancer resulted. Recently, employing a beta-carotene supplemented semi-defined diet, not only was no photoprotective effect found, but significant exacerbation of UV-carcinogenesis occurred. Earlier, a mechanism, based upon redox potential of interacting antioxidants, was proposed in which beta-carotene participated with vitamins E and C to efficiently repair oxy radicals and, thus, thought to provide photoprotection. In this schema, alpha-tocopherol would first intercept an oxy radical. In terminating the radical-propagating reaction, the tocopherol radical cation is formed which, in turn, is repaired by beta-carotene to form the carotenoid radical cation. This radical is repaired by ascorbic acid (vitamin C). As the carotenoid radical cation is a strongly oxidizing radical, unrepaired it could contribute to the exacerbating effect on UV-carcinogenesis. Thus, vitamin C levels could influence the levels of the pro-oxidant carotenoid radical cation. However, when hairless mice were fed beta-carotene supplemented semi-defined diet with varying levels of vitamin C (0-5590 mg kg(-1) diet) no effect on UV-carcinogenesis was observed. Lowering alpha-tocopherol levels did result in further increase of beta-carotene exacerbation, suggesting beta-carotene and alpha-tocopherol interaction. It was concluded that the non-injurious or protective effect of beta-carotene found in the closed-formula rations might depend on interaction with other dietary factors that are absent in the semi-defined diet. At present, beta-carotene use as a dietary supplement for photoprotection should be approached cautiously.     

Effects of an antioxidant-rich juice (sea buckthorn) on risk factors for coronary heart disease in humans

There is increasing evidence to support the hypothesis that free radical-mediated oxidative processes contribute to atherogenesis. More recently the ability of antioxidant nutrients to affect cell response and gene expression has been reported in vitro, providing a novel mechanistic perspective for the biological activity of antioxidants. Sea buckthorn (Hippopha? rhamnoides L.) is a rich source of antioxidants both aqueous and lipophilic, as well as polyunsaturated fatty acids. The objective of the study was to characterize the antioxidant profile of Sea buckthorn juice (SBJ) and to evaluate its effect on plasma lipids, LDL oxidation, platelet aggregation and plasma soluble cell adhesion protein concentration. Twenty healthy male volunteers were given either a placebo or SBJ for 8 weeks. Additional daily intakes of vitamin C, alpha-tocopherol, beta-carotene and flavonoids through SBJ supplementation were 462, 3.2, 1.0 and 355 mg respectively. There were no significant changes in plasma total cholesterol, LDL-C, platelet aggregation or plasma intercellular cell adhesion molecule 1 (ICAM-1) levels between treatment groups. Although not significant, a 20% and 17% increase in plasma HDL-C and triacylglycerol (TAG) concentrations were observed. SBJ supplementation also resulted in a moderate decrease in the susceptibility of LDL to oxidation.     

A role for reduced coenzyme Q in atherosclerosis?

Substantial evidence implicates oxidative modification of low density lipoprotein (LDL) as an important event contributing to atherogenesis. As a result, the elucidation of the molecular mechanisms by which LDL is oxidized and how such oxidation is prevented by antioxidants has been a significant research focus. Studies on the antioxidation of LDL lipids have focused primarily on alpha-tocopherol (alpha-TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. In addition to alpha-TOH, plasma LDL also contains low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q10). Recent studies have shown that in oxidizing plasma lipoproteins alpha-TOH can exhibit anti- or pro-oxidant activities for the lipoprotein's lipids exposed to a vast array of oxidants. This article reviews the molecular action of alpha-TOH in LDL undergoing "mild" radical-initiated lipid peroxidation, and discusses how small levels of CoQ10H2 can represent an efficient antioxidant defence for lipoprotein lipids. We also comment on the levels alpha-TOH, CoQ10H2 and lipid oxidation products in the intima of patients with coronary artery disease and report on preliminary studies examining the effect of coenzyme Q10 supplementation on atherogenesis in apolipoprotein E knockout mice.