ß-Carotene from the Alga Dunaliella bardawil Decreases Gene Expression of Adipose Tissue Macrophage Recruitment Markers and Plasma Lipid Concentrations in Mice Fed a High-Fat Diet.

Vitamin A and provitamin A carotenoids are involved in the regulation of adipose tissue metabolism and inflammation. We examined the effect of dietary supplementation using all-trans and 9-cis ß-carotene-rich Dunaliella bardawil alga as the sole source of vitamin A on obesity-associated comorbidities and adipose tissue dysfunction in a diet-induced obesity mouse model. Three-week-old male mice (C57BL/6) were randomly allocated into two groups and fed a high-fat, vitamin A-deficient diet supplemented with either vitamin A (HFD) or ß-carotene (BC) (HFD-BC). Vitamin A levels in the liver, WATs, and BAT of the HFD-BC group were 1.5-2.4-fold higher than of the HFD group. BC concentrations were 5-6-fold greater in BAT compared to WAT in the HFD-BC group. The eWAT mRNA levels of the Mcp-1 and Cd68 were 1.6- and 2.1-fold lower, respectively, and the plasma cholesterol and triglyceride concentrations were 30% and 28% lower in the HFD-BC group compared with the HFD group. Dietary BC can be the exclusive vitamin A source in mice fed a high-fat diet, as shown by the vitamin A concentration in the plasma and tissues. Feeding BC rather than vitamin A reduces adipose tissue macrophage recruitment markers and plasma lipid concentrations.

Dietary ß-Carotene Rescues Vitamin A Deficiency and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice.

Vitamin A deficiency (VAD) is a major health problem, especially in developing countries. In this study, we investigated the effect of VAD from weaning to adulthood in apoE-/- mice. Three-week-old male mice were allocated into four diet groups: I. VAD II. VAD+vitamin A (VA), 1500 IU retinyl-palmitate; III. VAD+ß-carotene (BC), 6 g/kg feed, containing 50% all-trans and 50% 9-cis BC. IV. VAD with BC and VA (BC+VA). After 13 weeks, we assessed the size of atherosclerotic plaques and measured VA in tissues and BC in plasma and tissues. VAD resulted in diminished hepatic VA levels and undetectable brain VA levels compared to the other groups. BC completely replenished VA levels in the liver, and BC+VA led to a two-fold elevation of hepatic VA accumulation. In adipose tissue, mice fed BC+VA accumulated only 13% BC compared to mice fed BC alone. Atherosclerotic lesion area of BC group was 73% lower compared to VAD group (p < 0.05). These results suggest that BC can be a sole source for VA and inhibits atherogenesis.

Potential of New Isolates of Dunaliella Salina for Natural ß-Carotene Production.

The halotolerant microalga Dunaliella salina has been widely studied for natural ß-carotene production. This work shows biochemical characterization of three newly isolated Dunaliellasalina strains, DF15, DF17, and DF40, compared with D. salina CCAP 19/30 and D. salina UTEX 2538 (also known as D. bardawil). Although all three new strains have been genetically characterized as Dunaliella salina strains, their ability to accumulate carotenoids and their capacity for photoprotection against high light stress are different. DF15 and UTEX 2538 reveal great potential for producing a large amount of ß-carotene and maintained a high rate of photosynthesis under light of high intensity; however, DF17, DF40, and CCAP 19/30 showed increasing photoinhibition with increasing light intensity, and reduced contents of carotenoids, in particular ß-carotene, suggesting that the capacity of photoprotection is dependent on the cellular content of carotenoids, in particular ß-carotene. Strong positive correlations were found between the cellular content of all-trans ß-carotene, 9-cis ß-carotene, all-trans α-carotene and zeaxanthin but not lutein in the D. salina strains. Lutein was strongly correlated with respiration in photosynthetic cells and strongly related to photosynthesis, chlorophyll and respiration, suggesting an important and not hitherto identified role for lutein in coordinated control of the cellular functions of photosynthesis and respiration in response to changes in light conditions, which is broadly conserved in Dunaliella strains. Statistical analysis based on biochemical data revealed a different grouping strategy from the genetic classification of the strains. The significance of these data for strain selection for commercial carotenoid production is discussed.

9-cis ß-Carotene Increased Cholesterol Efflux to HDL in Macrophages.

Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-ß-carotene (9-cis-ßc) is a precursor for 9-cis-retinoic-acid (9-cis-RA), which regulates macrophage cholesterol efflux. Our objective was to assess whether 9-cis-ßc increases macrophage cholesterol efflux and induces the expression of cholesterol transporters. Enrichment of a mouse diet with ßc from the alga Dunaliella led to ßc accumulation in peritoneal macrophages. 9-cis-ßc increased the mRNA levels of CYP26B1, an enzyme that regulates RA cellular levels, indicating the formation of RA from ßc in RAW264.7 macrophages. Furthermore, 9-cis-ßc, as well as all-trans-ßc, significantly increased cholesterol efflux to high-density lipoprotein (HDL) by 50% in RAW264.7 macrophages. Likewise, food fortification with 9-cis-ßc augmented cholesterol efflux from macrophages ex vivo. 9-cis-ßc increased both the mRNA and protein levels of ABCA1 and apolipoprotein E (APOE) and the mRNA level of ABCG1. Our study shows, for the first time, that 9-cis-ßc from the diet accumulates in peritoneal macrophages and increases cholesterol efflux to HDL. These effects might be ascribed to transcriptional induction of ABCA1, ABCG1, and APOE. These results highlight the beneficial effect of ßc in inhibition of atherosclerosis by improving cholesterol efflux from macrophages.

Vitamin A-deficient diet accelerated atherogenesis in apolipoprotein E(-/-) mice and dietary ß-carotene prevents this consequence.

Vitamin A is involved in regulation of glucose concentrations, lipid metabolism, and inflammation, which are major risk factors for atherogenesis. However, the effect of vitamin A deficiency on atherogenesis has not been investigated. Therefore, the objective of the current study was to examine whether vitamin A deficiency accelerates atherogenesis in apolipoprotein E-deficient mice (apoE(-/-)). ApoE(-/-) mice were allocated into the following groups: control, fed vitamin A-containing chow diet; BC, fed chow diet fortified with Dunaliella powder containing ßc isomers; VAD, fed vitamin A-deficient diet; and VAD-BC group, fed vitamin A-deficient diet fortified with a Dunaliella powder. Following 15 weeks of treatment, liver retinol concentration had decreased significantly in the VAD group to about 30% that of control group. Vitamin A-deficient diet significantly increased both plasma cholesterol concentrations and the atherosclerotic lesion area at the aortic sinus (+61%) compared to the control group. Dietary ßc fortification inhibited the elevation in plasma cholesterol and retarded atherogenesis in mice fed the vitamin A-deficient diet. The results imply that dietary vitamin A deficiency should be examined as a risk factor for atherosclerosis and that dietary ßc, as a sole source of retinoids, can compensate for vitamin A deficiency.

The inhibition of macrophage foam cell formation by 9-cis ß-carotene is driven by BCMO1 activity.

Atherosclerosis is a major cause of morbidity and mortality in developed societies, and begins when activated endothelial cells recruit monocytes and T-cells from the bloodstream into the arterial wall. Macrophages that accumulate cholesterol and other fatty materials are transformed into foam cells. Several epidemiological studies have demonstrated that a diet rich in carotenoids is associated with a reduced risk of heart disease; while previous work in our laboratory has shown that the 9-cis ß-carotene rich alga Dunaliella inhibits atherogenesis in mice. The effect of 9-cis ß-carotene on macrophage foam cell formation has not yet been investigated. In the present work, we sought to study whether the 9-cis ß-carotene isomer, isolated from the alga Dunaliella, can inhibit macrophage foam cell formation upon its conversion to retinoids. The 9-cis ß-carotene and Dunaliella lipid extract inhibited foam cell formation in the RAW264.7 cell line, similar to 9-cis retinoic acid. Furthermore, dietary enrichment with the algal powder in mice resulted in carotenoid accumulation in the peritoneal macrophages and in the inhibition of foam cell formation ex-vivo and in-vivo. We also found that the ß-carotene cleavage enzyme ß-carotene 15,15'-monooxygenase (BCMO1) is expressed and active in macrophages. Finally, 9-cis ß-carotene, as well as the Dunaliella extract, activated the nuclear receptor RXR in hepa1-6 cells. These results indicate that dietary carotenoids, such as 9-cis ß-carotene, accumulate in macrophages and can be locally cleaved by endogenous BCMO1 to form 9-cis retinoic acid and other retinoids. Subsequently, these retinoids activate the nuclear receptor RXR that, along with additional nuclear receptors, can affect various metabolic pathways, including those involved in foam cell formation and atherosclerosis.

Prevention of atherosclerosis progression by 9-cis-ß-carotene rich alga Dunaliella in apoE-deficient mice.

INTRODUCTION: ß-Carotene-rich diet has been shown to be inversely associated with the risk of coronary heart disease. However, clinical trials using synthetic all-trans-ß-carotene failed to demonstrate a beneficial effect. We therefore sought to study the effect of natural source of ß-carotene, the alga Dunaliella, containing both all-trans and 9-cis-ß-carotene on atherosclerosis. In a previous study we showed that 9-cis-ß-carotene-rich powder of the alga Dunaliella inhibits early atherogenesis in low-density lipoprotein receptor knockout mice. AIMS: The aims of the current work were to study whether diet enriched with Dunaliella powder would inhibit the progression of established atherosclerosis in old male apoE-deficient mice and to compare the effect of Dunaliella on lipid profile and atherosclerosis in a low-versus high-fat diet fed mice. METHODS: In the first experiment, young mice (12 weeks old) were allocated into 3 groups: (1) low-fat diet; (2) low-fat diet + Dunaliella powder (8%); (3) low-fat diet + ß-carotene-deficient Dunaliella. In the second experiment, old mice (7 months old) with established atherosclerotic lesions were allocated into 4 groups: (1) low-fat diet; (2) low-fat diet + Dunaliella; (3) high fat-diet; (4) high-fat diet + Dunaliella. RESULTS: In young mice fed a low-fat diet, a trend toward lower atherosclerotic lesion area in the aortic sinus was found in the Dunaliella group compared with the control group. In old mice with established atherosclerotic lesion, Dunaliella inhibited significantly plasma cholesterol elevation and atherosclerosis progression in mice fed a high-fat diet. CONCLUSION: The results of this study suggest that a diet containing natural carotenoids, rich in 9-cis-ß-carotene, has the potential to inhibit atherosclerosis progression, particularly in high-fat diet regime.

Algae biodiesel life cycle assessment using current commercial data.

Autotrophic microalgae represent a potential feedstock for transportation fuels, but life cycle assessment (LCA) studies based on laboratory-scale or theoretical data have shown mixed results. We attempt to bridge the gap between laboratory-scale and larger scale biodiesel production by using cultivation and harvesting data from a commercial algae producer with ∼1000 m(2) production area (the base case), and compare that with a hypothetical scaled up facility of 101,000 m(2) (the future case). Extraction and separation data are from Solution Recovery Services, Inc. Conversion and combustion data are from the Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation Model (GREET). The LCA boundaries are defined as "pond-to-wheels". Environmental impacts are quantified as NER (energy in/energy out), global warming potential, photochemical oxidation potential, water depletion, particulate matter, and total NOx and SOx. The functional unit is 1 MJ of energy produced in a passenger car. Results for the base case and the future case show an NER of 33.4 and 1.37, respectively and GWP of 2.9 and 0.18 kg CO2-equivalent, respectively. In comparison, petroleum diesel and soy diesel show an NER of 0.18 and 0.80, respectively and GWP of 0.12 and 0.025, respectively. A critical feature in this work is the low algal productivity (3 g/m(2)/day) reported by the commercial producer, relative to the much higher productivities (20-30 g/m(2)/day) reported by other sources. Notable results include a sensitivity analysis showing that algae with an oil yield of 0.75 kg oil/kg dry biomass in the future case can bring the NER down to 0.64, more comparable with petroleum diesel and soy biodiesel. An important assumption in this work is that all processes are fully co-located and that no transport of intermediate or final products from processing stage to stage is required.

Bio-diesel production directly from the microalgae biomass of Nannochloropsis by microwave and ultrasound radiation.

This work offers an optimized method for the direct conversion of harvested Nannochloropsis algae into bio-diesel using two novel techniques. The first is a unique bio-technology-based environmental system utilizing flue gas from coal burning power stations for microalgae cultivation. This method reduces considerably the cost of algae production. The second technique is the direct transesterification (a one-stage method) of the Nannochloropsis biomass to bio-diesel production using microwave and ultrasound radiation with the aid of a SrO catalyst. These two techniques were tested and compared to identify the most effective bio-diesel production method. Based on our results, it is concluded that the microwave oven method appears to be the most simple and efficient method for the one-stage direct transesterification of the as-harvested Nannochloropsis algae.

Carotenoids provide the major antioxidant defence in the globally significant N2-fixing marine cyanobacterium Trichodesmium.

Photosynthetic oxygen-evolving microorganisms contend with continuous self-production of molecular oxygen and reactive oxygen species. The deleterious effects of reactive oxygen species are exacerbated for cyanobacterial nitrogen-fixers (diazotrophs) due to the innate sensitivity of nitrogenase to oxygen. This renders incompatible the processes of oxygen-evolving photosynthesis and N-fixation. We examined total antioxidative potential of various diazotrophic and non-diazotrophic cyanobacteria. We focused on Trichodesmium spp., a bloom-forming marine diazotroph that contributes significantly to global nitrogen fixation. Among the species tested, Trichodesmium possessed the highest antioxidant activity. Moreover, while proteins constituted the dominant antioxidative component of all other cyanobacteria tested, Trichodesmium was unique in that small-molecule natural products provided the majority of antioxidant activity, while proteins constituted only 13% of total antioxidant activity. Bioassay-guided fractionation followed by high-performance liquid chromatography profiling of antioxidant purified fractions identified the highly potent antioxidant all-trans-ß-carotene, and small amounts of 9-cis-ß-carotene and retinyl palmitate. Search of the Trichodesmium genome identified protein sequences homologous to key enzymes in the ß-carotene to retinyl palmitate biosynthetic pathway, including 33-37% identity to lecithin retinol acyltransferase. The present study demonstrates the importance of carotenoids in Trichodesmium's arsenal of defensive compounds against oxidative damage and protection of nitrogenase from oxygen and its radicals.

The effect of tomato-derived lycopene on low carotenoids and enhanced systemic inflammation and oxidation in severe obesity.

BACKGROUND: Fat tissue mediates the production of inflammatory cytokines and oxidative products, which are key steps in the development of type 2 diabetes and atherosclerosis. Antioxidant-rich diets protect against chronic diseases. Antioxidants may interfere with pro-inflammatory signals. OBJECTIVES: To investigate the effect of the potent tomato-derived antioxidant carotenoid, lycopene, on plasma antioxidants (carotenoids and vitamin E), inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) and oxidation products (conjugated dienes). METHODS: Eight obese patients (body mass index 37.5 +/- 2.5 kg/m2) were compared with a control group of eight lean, age and gender-matched subjects (BMI 21.6 +/- 0.6 kg/m2), before and after 4 weeks of lycopene supplementation (tomato-derived Lyc-O-Mato) (30 mg daily). RESULTS: Plasma carotenoids were significantly reduced in the obese compared to control subjects (0.54 +/- 0.06 vs. 0.87 +/- 0.08 microg/ml, P < 0.01). CRP levels were significantly higher (6.5 vs. 1.1 mg/L, P = 0.04) in obese vs. controls, as were IL-6 and conjugated dienes (3.6 and 7.9-fold, respectively). CRP, IL-6 and conjugated dienes correlated with BMI, while IL-6 and conjugated dienes correlated inversely with carotenoids (P < 0.05). Following lycopene treatment, a significant elevation of plasma carotenoids (1.79 vs. 0.54 microg/ml) and specifically lycopene (1.15 vs 0.23 microg/ml) (P < 0.001) occurred in the treatment vs. the placebo group, respectively. Markers of inflammation and oxidation products were not altered by lycopene. CONCLUSIONS: Obese patients showed abnormally higher markers of inflammation and oxidation products and lower plasma carotenoids. The lack of reduction of pro-inflammatory markers could be attributed to the short period of the study and the small number of participants. More studies are needed on the protective qualities of natural antioxidant-rich diets against obesity-related co-morbidities.

A 9-cis beta-carotene-enriched diet inhibits atherogenesis and fatty liver formation in LDL receptor knockout mice.

Our aim was to study the effect of 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil on lipid profile, atherogenesis, and liver steatosis in high-fat diet-fed LDL receptor knockout mice. In 4 sets of experiments, mice were distributed into the following groups: control, fed an unfortified diet; Dunaliella 50, fed a diet composed of 50% 9-cis and 50% all-trans beta-carotene; Dunaliella 25, fed a diet containing 25% 9-cis and 75% all-trans beta-carotene; beta-carotene-deficient Dunaliella, fed beta-carotene-deficient Dunaliella powder; and all-trans beta-carotene, fed a synthetic all-trans beta-carotene. All fortified diets contained 0.6% total beta-carotene. Algal 9-cis beta-carotene was absorbed by the mice and accumulated in the liver. Synthetic all-trans beta-carotene was not converted to 9-cis beta-carotene. Dunaliella 50 inhibited high-fat diet-induced plasma cholesterol elevation by 40-63% and reduced cholesterol concentrations in the atherogenic VLDL and LDL. Atherosclerotic lesion area in mice treated with Dunaliella 50 was 60-83% lower compared with mice fed the high-fat diet alone. beta-Carotene-deficient Dunaliella did not influence plasma cholesterol and atherogenesis, suggesting that beta-carotene is essential for a Dunaliella protective effect. Moreover, by administrating Dunaliella powder containing different levels of 9-cis and all-trans beta-carotene isomers, we found that the effect on plasma cholesterol concentration and atherogenesis is 9-cis-dependent. Dunaliella 50 also inhibited fat accumulation and inflammation in the livers of mice fed a high-fat diet, which was accompanied by reduced mRNA levels of inflammatory genes. These results in mice suggest that 9-cis beta-carotene may have the potential to inhibit atherogenesis in humans.

A carotenoid algal preparation containing phytoene and phytofluene inhibited LDL oxidation in vitro.

The antioxidative effect of the carotenoids phytoene and phytofluene in biological systems has not yet been studied. We therefore sought to investigate the effect of these carotenoids, isolated from the alga Dunaliella bardawil, in a biological system and used the in vitro low density lipoprotein (LDL) oxidation method to assay their antioxidative effects. We found that similar to beta-carotene and alpha-tocopherol, a carotenoid algal preparation containing phytoene and phytofluene inhibited LDL oxidation. These findings and the presence of phytoene and phytofluene in human tissues suggest that they can be part of the defense system against oxidative stress.

Exhaustive exercise modifies oxidative stress in smoking subjects.

BACKGROUND: Exhaustive exercise is associated with increased metabolic rate and accelerated generation of reactive oxygen species. Cigarette smoke also contains oxidants that may participate in the development of atherosclerosis. However, data on the association between exercise and smoking are sparse. METHODS: A homogenous group of 30 young men (15 smokers and 15 nonsmokers; mean age, 23.7 +/- 2.6 years), healthy, trained subjects, were assessed before and after a standard maximal exercise test. RESULTS: Exercise led to increased protein oxidation (carbonyl assay) in both smokers (+17.7%, P < 0.001) and nonsmokers (+19.1%, P < 0.05), elevation in plasma conjugated dienes (+ 157%, P < 0.04), and plasma lipid peroxides (+14%, P < 0.059) in smokers versus nonsmokers after exercise. Plasma antioxidants levels were significantly lower in the smoking group, with reduction in total carotenoids (-36.5%, P < 0.001), vitamin A (-80%, P < 0.001), and vitamin E (-64%, P < 0.002), compared with nonsmokers. A significant rise in leakage of muscle enzymes (CPK, LDH) and urine proteins (microalbumin and myoglobin) occurred in all subjects after exercise. CRP levels were higher in smokers compared with nonsmokers before and after exercise. CONCLUSIONS: Our results suggest that unnoticed interaction exists between smoking and intense exercise, which indicates that smokers are more susceptible to oxidative insults probably due to lower antioxidant capacity.

9-cis beta-carotene-rich powder of the alga Dunaliella bardawil increases plasma HDL-cholesterol in fibrate-treated patients.

The effect of fibrates on high density lipoprotein (HDL)-cholesterol levels is suggested to be mediated by its binding to peroxisome proliferator-activated receptor-alpha (PPARalpha). Upon ligand binding, PPARalpha heterodimerizes with the 9-cis retinoic acid receptor (RXR) and it is this heterodimer which regulates gene expression. We assessed the hypothesis that a combined treatment with fibrate plus 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil, as a source of 9-cis retinoic acid, would improve the drug's effect on HDL-cholesterol levels. In an open-labeled first trial, 20 fibrate-treated men with plasma HDL-cholesterol levels below 40 mg/dl were given Dunaliella capsules, providing 60 mg beta-carotene/day, containing all-trans and 9-cis beta-carotene (1:1 ratio, w/w). Twenty-two fibrate-treated patients participated in a double-blind placebo-controlled second trial. Eleven patients were treated with Dunaliella capsules, and 11 patients were treated with beta-carotene-deficient Dunaliella capsules. Following 6 weeks of the dual treatment plasma HDL-cholesterol increased by 24.5 and 12.7% in the first and second trials, respectively (P=0.002 and 0.012). The dual treatment also increased HDL-cholesterol levels in human apolipoprotein A-I transgenic mice by 87.5% (P=0.021). The results show that a combination treatment of fibrate plus 9-cis beta-carotene-rich Dunaliella powder amplifies the effect of the drug on HDL-cholesterol levels.

Effect of a Mediterranean meal on postprandial carotenoids, paraoxonase activity and C-reactive protein levels.

BACKGROUND AND AIM: Atherosclerosis involves oxidative and inflammatory mediators regulated by fat and antioxidants. Therefore, we studied the postprandial evolution of plasma lipids, carotenoids, C-reactive protein (CRP), and human serum paraoxanase activity (PON1) following two different fatty meals. SUBJECTS AND METHODS: Eight healthy males consumed a 45% fat 1,000 Kcal Mediterranean-like (Med) meal (monounsaturated 61% of fat) compared to a Western-like (Wes) (saturated 57% of fat) meal. Blood was collected at baseline (time 0) 2, 4 and 7 h postprandial. Plasma lipids, glucose, insulin, total carotenoids, CRP, and PON1 were analyzed. RESULTS: There was a marginal increase in cholesterol and glucose after both meals. Triglycerides increased modestly (to less than 200 mg/dl) and insulin increased (more in the Wes-like meal) but still within normal range, indicating a low glycemic index for both meals. Only the Med-like meal resulted in a significant increase in both PON1 activity (16%, p < 0.02) and carotenoids (74%, p < 0.02) with a 2-hour postprandial decrease in CRP (6%, p < 0.02). CONCLUSION: A postprandial monounsaturated fatty acid rich meal increases both plasma carotenoids and PON1 with a decrease in CRP levels, thus providing a novel potential explanation to the protective properties of a Mediterranean diet against atherogenesis.

Effect of lycopene supplementation on lung function after exercise in young athletes who complain of exercise-induced bronchoconstriction symptoms.

BACKGROUND: It has been suggested that exercise-induced bronchoconstriction may involve oxidative stress. Strenuous exercise promotes free radical production, which can lead to many of the pathophysiologic changes associated with asthma, including bronchoconstriction, mucus secretion, and microvascular leakage. Lycopene has been shown to have high antioxidative activity. OBJECTIVE: To evaluate the effect of lycopene supplementation on airway hyperreactivity and inflammation in young athletes who complain of difficulty in breathing related to physical exertion. METHODS: Nineteen young athletes with exercise-related difficulty in breathing visited the exercise laboratory 3 times. During the first visit, participants underwent a baseline evaluation of exercise-induced bronchoconstriction. Daily for 1 week before each of the 2 subsequent visits, participants ingested 30 mg of lycopene (a natural antioxidant) or placebo (in randomized order, double-blind). A 2-week washout period was given between each visit. During each visit, lung functions were evaluated before and after an 8-minute run on the treadmill (85% of the predicted maximal heart rate). RESULTS: There was no difference in the mean+/-SD decrease in forced expiratory volume in 1 second after exercise during lycopene treatment compared with placebo treatment (11.8%+/-12.5% and 11.0%+/-11.6%). In addition, there was no apparent division into responders and nonresponders. CONCLUSION: A daily dose of lycopene for 1 week does not affect lung function after exercise and may not provide any protective effect against clinical difficulty in breathing in young athletes.

Low plasma antioxidants and normal plasma B vitamins and homocysteine in patients with severe obesity.

BACKGROUND: Obesity is among the well-established risk factors for cardiovascular morbidity and mortality. However, the exact mechanisms are not well understood. Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are linked to accelerated atherosclerosis through increased oxidative stress and homocysteine. OBJECTIVE: To compare plasma antioxidant vitamins (carotenoids and vitamin E), B vitamins (folic acid and B12) and homocysteine--all linked to increased cardiovascular morbidity--between patients with severe obesity and lean control subjects. METHODS: We investigated plasma carotenoids, vitamin E, folic acid, B12, and homocysteine in 25 obese patients and their age-matched controls (body mass index 38 +/- 3 vs. 21 +/- 2 kg/m2), respectively), related to BMI and plasma insulin. RESULTS: Patients with obesity had normal B vitamins and a non-significant decrease in plasma homocysteine as compared to controls (9.4 +/- 2.6 vs. 11.4 +/- 4.8 mumol/L, P = 0.07). There was a significant decrease in both plasma carotenoids and vitamin E (0.69 +/- 0.32 vs. 1.25 +/- 0.72 and 24 +/- 10 vs. 33 +/- 14 micrograms/ml, respectively; P < 0.01). Both vitamins were inversely related to BMI and plasma insulin, which was significantly increased in patients with obesity (22 +/- 21 vs. 6 +/- 2 microU/ml, P < 0.01). CONCLUSIONS: Obese patients with BMI above 35 kg/m2 show low plasma antioxidants (carotenoids and vitamin E). This may result in increased oxidative stress and consequently enhanced atherosclerosis in these patients.

[Plasma anti-oxidants and rheumatoid arthritis].

We present a clinical study aimed to compare plasma antioxidant vitamins, vitamin E, beta-carotene and vitamin A. The study consisted of a group (15 patients) with rheumatoid arthritis (RA) compared to a healthy control group. There was a significant decrease in plasma vitamin E, beta-carotene and vitamin A (vitamin E 30.4 +/- 4.9 VS 43.6 +/- 8.2 micrograms/ml, beta-carotene 0.73 +/- 0.26 VS 1.02 +/- 0.22 micrograms/ml and vitamin A 0.22 +/- 0.07 VS 0.46 +/- 0.15 microgram/ml, P < 0.01 patients VS control, respectively). Supplementation of Dunaliella (natural)--beta-carotene to the RA patients for 3 weeks, resulted in a significant increase in plasma vitamin E (47.9 +/- 5.5 micrograms/ml) beta-carotene (0.87 +/- 0.21 microgram/ml) and vitamin A (0.55 +/- 0.15 microgram/ml). There were no changes in the activity indexes of RA. Low plasma antioxidant vitamins in patients with RA are consistent with the observation that oxidative processes occur in the inflammed joints. The validity of antioxidant vitamins as supplementary therapy for RA is not clear.

Bioavailability of the isomer mixture of phytoene and phytofluene-rich alga Dunaliella bardawil in rat plasma and tissues.

Dunaliella bardawil, a beta-carotene-accumulating alga was treated by the bleaching herbicide norflurazon to select sub-species rich with a mixture of 9-cis and all-trans stereoisomers of phytoene and phytofluene. The present study determines the bioavailability of phytoene and phytofluene with their stereoisomers in rats fed on a diet supplemented with Dunaliella phytoene-rich spray dried powder. Three groups of female weanling rats, eight animals each, were fed AIN diets for two weeks. The control consumed the diet as is. The experimental group was supplemented with 50 g Dunaliella powder to give phytoene/phytofluene at a level of 1 g/kg diet, and the placebo was provided with the oxidized algae free of carotenoids at the same amount. Weight gain and tissues weight of rats fed on the control diet, or on the experimental diets were statistically same. Tissue analyses were carried out by liquid chromatography at the end of two weeks feeding for vitamin A, carotenoids, phytoene and phytofluene and theirs stereoisomers. Liver analyses revealed high hepatic storage of phytoene in the experimental group. Analysis of the other tissues, adrenal, brain, heart, kidney, lung, and spleen detected small amounts of phytoene in the adrenal, kidney and spleen and in the plasma. High-pressure liquid chromatography for stereoisomeric composition was performed to all phytoene-containing tissues. The original algal diet content of 9-cis-to-all-trans ratio of 1:1 was maintained in the plasma and adrenal while in the liver, spleen and kidney the ratio was reduced to 1:3. The preferential accumulation of all-trans phytoene over 9-cis phytoene in the liver, spleen and kidney may be interpreted as indicating stronger antioxidative effect of 9-cis phytoene over the all-trans isomer or alternatively, in vivo streoisomerization of 9-cis phytoene to the all-trans structure.