Biomedical subjects

Robert M Russell

Publications and source records attributed to Robert M Russell.

At least 19 recordsLinked to original sources

PubMed2006

The biochemical characterization of ferret carotene-9',10'-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo.

Previous studies have shown that beta-carotene 15,15'-monooxygenase catalyzes the cleavage of beta-carotene at the central carbon 15,15'-double bond but cleaves lycopene with much lower activity. However, expressing the mouse carotene 9',10'-monooxygenase (CMO2) in beta-carotene/lycopene-synthesizing and -accumulating Escherichia coli strains leads to both a color shift and formation of apo-10'-carotenoids, suggesting the oxidative cleavage of both carotenoids at their 9',10'-double bond. Here we provide information on the biochemical characterization of CMO2 of the ferret, a model for human carotenoid metabolism, in terms of the kinetic analysis of beta-carotene/lycopene cleavage into beta-apo-10'-carotenal/apo-10'-lycopenal in vitro and the formation of apo-10'-lycopenoids in ferrets in vivo. We demonstrate that the recombinant ferret CMO2 catalyzes the excentric cleavage of both all-trans-beta-carotene and the 5-cis- and 13-cis-isomers of lycopene at the 9',10'-double bond but not all-trans-lycopene. The cleavage activity of ferret CMO2 was higher toward lycopene cis-isomers as compared with beta-carotene as substrate. Iron was an essential co-factor for the reaction. Furthermore, all-trans-lycopene supplementation in ferrets resulted in significant accumulation of cis-isomers of lycopene and the formation of apo-10'-lycopenol, as well as up-regulation of the CMO2 expression in lung tissues. In addition, in vitro incubation of apo-10'-lycopenal with the post-nuclear fraction of hepatic homogenates of ferrets resulted in the production of both apo-10'-lycopenoic acid and apo-10'-lycopenol, respectively, depending upon the presence of NAD+ or NADH as cofactors. Our finding of bioconversion of cis-isomers of lycopene into apo-10'-lycopenoids by CMO2 is significant because cis-isomers of lycopene are a predominant form of lycopene in mammalian tissues and apo-lycopenoids may have specific biological activities related to human health.

Amino Acid Sequence↗

PubMed2006

Induction of pulmonary neoplasia in the smoke-exposed ferret by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): a model for human lung cancer.

Research into dietary chemoprevention against lung carcinogenesis has been limited by the lack of appropriate animal models that closely mimic smoking-related human lung cancer. Ferrets (Mustela putorius furo) have been used to study the biologic activities of carotenoids against smoke-induced lung lesions, but this model has yet to be thoroughly established and validated. To determine the appropriateness of the ferret as a model for human lung cancer, we have performed a 6-month in vivo study in ferrets exposed to both tobacco smoke and a carcinogen (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) found in cigarette smoke. Results showed that six out 12 ferrets exposed to both NNK injection and cigarette smoke developed grossly identifiable lung tumors whereas none of nine ferrets from the sham treatment group developed any lung lesions. The histopathological types of these tumors (squamous cell carcinoma, adenosquamous carcinoma and adenocarcinoma) in ferret lungs are very similar to those in humans. In addition, 10 out of 12 ferrets exposed to both NNK and cigarette smoke developed preneoplastic lesions (squamous metaplasia, dysplasia, and atypical adenomatous hyperplasia) with complex growth patterns whereas the sham group did not show any of these lesions. Furthermore, the expression of proliferating cellular nuclear antigen increased markedly in both gross tumors and preneoplastic lesions in the lungs. In summary, the development of both preneoplastic lesions and gross lung tumors in ferrets provides an excellent and unique model for studying lung cancer chemoprevention with agents such as carotenoids, and for studying the molecular mechanism of carcinogenesis in the earlier stages of smoke-related lung cancer.

Adenocarcinoma↗

PubMed2006

Combined antioxidant (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation increases the levels of lung retinoic acid and inhibits the activation of mitogen-activated protein kinase in the ferret lung cancer model.

Interactions among beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (AA) led to the hypothesis that using a combination of these antioxidants could be more beneficial than using a single antioxidant alone, particularly against smoke-related lung cancer. In this investigation, we have conducted an animal study to determine whether combined BC, AT and AA supplementation (AOX) protects against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis in smoke-exposed (SM) ferrets. Ferrets were treated for 6 months in the following four groups: (i) control, (ii) SM + NNK, (iii) AOX and (iv) SM + NNK + AOX. Results showed that the combined AOX supplementation (i) prevented the SM + NNK-decreased lung concentrations of retinoic acid (RA) and BC; (ii) inhibited the SM + NNK-induced phosphorylation of Jun N-terminal kinase (JNK), extracellular-signal-regulated protein kinase (ERK) and proliferating cellular nuclear antigen proteins in the lungs of ferrets; and (iii) blocked the SM + NNK-induced up-regulation of total p53 and Bax proteins, as well as phosphorylated p53 in the lungs of ferrets. In addition, there were no lesions observed in the lung tissue of ferrets in the control and/or the AOX groups after 6 months of intervention, but combined AOX supplementation resulted in a trend toward lower incidence of both preneoplastic lung lesions and lung tumor formation in SM + NNK + AOX group of ferrets, as compared with the SM + NNK group alone. These data indicate that combined AOX supplementation could be a useful chemopreventive strategy against lung carcinogenesis through maintaining normal tissue levels of RA and inhibiting the activation of mitogen-activated protein kinase pathways, cell proliferation and phosphorylation of p53.

Animals↗

PubMed2006

Modification of lymphocyte DNA damage by carotenoid supplementation in postmenopausal women.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic diseases related to aging such as cancer and cardiovascular disease. Carotenoids could be a part of a protective strategy to minimize oxidative damage in vulnerable populations, such as the elderly. OBJECTIVE: Our aim was to determine the protective effect of carotenoids against DNA damage. DESIGN: A randomized, double-blind, placebo-controlled intervention study was conducted. Thirty-seven healthy, nonsmoking postmenopausal women aged 50-70 y were randomly assigned to 1 of 5 groups and were instructed to consume a daily dose of mixed carotenoids (beta-carotene, lutein, and lycopene; 4 mg each), 12 mg of a single carotenoid (beta-carotene, lutein, or lycopene), or placebo for 56 d. Plasma carotenoid concentrations were analyzed by using HPLC, and lymphocyte DNA damage was measured by using a single-cell gel electrophoresis (comet) assay. RESULTS: At day 57, all carotenoid-supplemented groups showed significantly lower endogenous DNA damage than at baseline (P < 0.01), whereas the placebo group did not show any significant change. Significantly less (P < 0.05) endogenous DNA damage was found as early as day 15 in the mixed carotenoid (P < 0.01) and beta-carotene (P < 0.05) groups. CONCLUSIONS: The results indicate that carotenoid supplementation decreases DNA damage and that a combination of carotenoids (4 mg each of lutein, beta-carotene, and lycopene), an intake that can be achieved by diet, or a larger dose (12 mg) of individual carotenoids exerts protection against DNA damage.

Aged↗

PubMed2006

Lycopene supplementation prevents smoke-induced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets.

Cigarette smoking increases the risk for gastric cancer. Higher intakes or blood levels of lycopene are associated with a decreased risk of gastric cancer. However, the biological mechanisms by which lycopene may protect against gastric carcinogenesis are poorly understood. We evaluated the effects of lycopene supplementation on smoke-induced changes in protein levels of p53, p53 target genes (p21(Waf1/Cip1) and Bax-1), cell proliferation, and apoptosis in the gastric mucosa of ferrets. Ferrets were assigned to cigarette smoke exposure or to no exposure and to no, low-dose, or high-dose lycopene supplementation (2 x 3 factorial design) for 9 wk. Lycopene concentrations were significantly elevated in a dose-dependent manner in the gastric mucosa of ferrets supplemented with lycopene alone, but were markedly reduced in ferrets supplemented with lycopene and exposed to smoke. Although ferrets were given lycopene containing 95% all-trans isomers, cis isomers were the predominant forms in the gastric mucosa. Total p53 and phosphorylated p53 levels were greater in ferrets exposed to smoke alone than in all other groups. Levels were approximately 300 and 500% of the controls, respectively. However, smoke-elevated total p53 and phosphorylated p53 were markedly attenuated by both doses of lycopene. p21(Waf1/Cip1), Bax-1, and cleaved caspase 3 were substantially decreased, whereas cyclin D1 and proliferating cellular nuclear antigen (PCNA) were increased in ferrets exposed to smoke alone. Lycopene prevented smoke-induced changes in p21(Waf1/Cip1), Bax-1, cleaved caspase 3, cyclin D1, and PCNA in a dose-dependent fashion. These data indicate that lycopene may prevent smoke exposure-induced changes in p53, p53 phosphorylation, p53 target genes, cell proliferation, and apoptosis in the gastric mucosa of ferrets.

Animals↗

PubMed2005

Essential nutrients: food or supplements? Where should the emphasis be?

The consumption of adequate levels and proper balance of essential nutrients is critical for maintaining health. The identification, isolation, and purification of nutrients in the early 20th century raised the possibility that optimal health outcomes could be realized through nutrient supplementation. Recent attempts using this approach for cardiovascular disease and lung cancer have been disappointing, as demonstrated with vitamin E and beta carotene. Moreover, previously unrecognized risks caused by nutrient toxicity and nutrient interactions have surfaced during intervention studies. The most promising data in the area of nutrition and positive health outcomes relate to dietary patterns, not nutrient supplements. These data suggest that other factors in food or the relative presence of some foods and the absence of other foods are more important than the level of individual nutrients consumed. Finally, unknown are the implications on public health behavior of shifting the emphasis away from food toward nutrient supplements. Notwithstanding the justification for targeting recommendations for nutrient supplements to certain segments of the population (eg, the elderly), there are insufficient data to justify an alteration in public health policy from one that emphasizes food and diet to one that emphasizes nutrient supplements.

Biomedical Research↗

PubMed2005

Bioavailability of synthetic and biosynthetic deuterated lycopene in humans.

Current knowledge of the bioavailability of lycopene in humans is limited due to the inability to distinguish newly administered lycopene from the body reserves of lycopene. A quantitative method to assess the absorption and relative bioavailability of newly absorbed synthetic or natural lycopene was developed using two deuterated lycopene sources, in conjunction with an advanced LC/APCI-MS (liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry) to analyze newly absorbed lycopene in blood samples of study subjects. Two subjects (1 male and 1 female) consumed hydroponically grown tomatoes containing deuterium-enriched lycopene (80-84 g wet weight tomato containing 16.3 and 17.4 micromol lycopene, respectively) and two subjects (1 male, and 1 female) consumed 11 micromol synthetic (2)H(10) lycopene in 6 g of corn oil. Tomatoes were steamed and pureed. The doses were given together with a liquid formulated drink with 25% energy from fat. Our results showed that up to 34 days after taking an oral (2)H(10) lycopene dose (synthetic or from tomato) with a liquid formula drink, the area under the curve of the average serum percent enrichment response of synthetic lycopene reached 33.9 (+/-1.7) nmol-day/micromol lycopene in the dose, whereas that of lycopene from the tomato dose was 11.8 (+/-0.3) nmol-day/mumol lycopene in the dose. Our study provides evidence that the absorption of physiological levels of lycopene in intrinsically labeled tomatoes can be studied in humans. From these preliminary investigations, we find that the bioavailability of synthetic lycopene in oil appears to be about three times higher than that of lycopene from steamed and pureed tomatoes.

Biological Availability↗

PubMed2005

Spinach or carrots can supply significant amounts of vitamin A as assessed by feeding with intrinsically deuterated vegetables.

BACKGROUND: The vitamin A value of spinach and carrots needs to be measured directly. OBJECTIVE: The objective was to determine the vitamin A value of intrinsically labeled dietary spinach and carrots in humans. DESIGN: Spinach and carrots were intrinsically labeled by growing these plants in 25 atom% 2H2O nutrient solution. Growth in this medium yielded a range of trans beta-carotene (tbeta-carotene) isotopomers with a peak enrichment at molecular mass plus 10 mass units. Seven men with a mean (+/-SD) age of 59.0 +/- 6.3 y and a body mass index (in kg/m2) of 25.7 +/- 1.5 consumed puréed spinach (300 g, 20.8 micromol tbeta-carotene equivalents) or carrots (100 g, 19.2 micromol tbeta-carotene equivalents) with a standardized liquid diet (no extra fiber) in random order 4 mo apart. Seven women with a mean (+/-SD) age of 55.5 +/- 6.3 y and a body mass index of 26.4 +/- 4.2 consumed puréed spinach only (300 g, 20.0 micromol tbeta-carotene equivalents). A reference dose of [13C8]retinyl acetate (8.9 micromol) in oil was given to each subject 1 wk after each vegetable dose. Blood samples were collected over 35 d. RESULTS: Areas under the curve for total labeled serum beta-carotene responses were 42.4 +/- 8.5 nmol.d per micromol spinach beta-carotene and 119.8 +/- 23.0 nmol.d per micromol carrot beta-carotene (P < 0.01). Compared with the [13C8]retinyl acetate reference dose, spinach tbeta-carotene conversion to retinol was 20.9 +/- 9.0 to 1 (range: 10.0-46.5 to 1) and carrot tbeta-carotene conversion to retinol was 14.8 +/- 6.5 to 1 (range: 7.7-24.5 to 1) by weight. CONCLUSIONS: Spinach and carrots can provide a significant amount of vitamin A even though the amount is not as great as previously proposed. Food matrices greatly affect the bioavailability of plant carotenoids, their efficiency of conversion to vitamin A, or both.

Aged↗

PubMed2005

Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys.

PURPOSE: Macular pigment (MP) is composed of the xanthophylls lutein (L) and zeaxanthin (Z) and may help to prevent age-related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls. METHODS: From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 micromol/kg per day for 24 to 101 weeks. At baseline and at 4- to 12-week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina (central 4 mm, 8-mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet. RESULTS: Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R,3'S-Z (RSZ or meso-Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula (central 4 mm). All-trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z. CONCLUSIONS: L is the precursor of RSZ, a major component of macular pigment. Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion.

Adipose Tissue↗

PubMed2004

Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compartments of human plasma.

Antioxidants located in both the hydrophilic and lipophilic compartments of plasma are actively involved as a defense system against reactive oxygen species (ROS), which are continuously generated in the body due to both normal metabolism and disease. However, when the production of ROS is not controlled, it leads to cellular lipid, protein, and DNA damage in biological systems. Several assays to measure 'total' antioxidant capacity of plasma have been developed to study the involvement of oxidative stress in pathological conditions and to evaluate the functional bioavailability of dietary antioxidants. Conventional assays to determine antioxidant capacity primarily measure the antioxidant capacity in the aqueous compartment of plasma. Consequently, water-soluble antioxidants such as ascorbic acid, uric acid and protein thiols mainly influence these assays, whereas fat-soluble antioxidants such as tocopherols and carotenoids play only a minor role. However, there are active interactions among antioxidants located in the hydrophilic and lipophilic compartments of plasma. Therefore, new approaches to define the 'true' total antioxidant capacity of plasma should reflect the antioxidant network between water- and fat-soluble antioxidants in plasma. Revelation of the mechanism of action of antioxidants and their true antioxidant potential will help us to optimize the antioxidant defenses in the body.

Antioxidants↗

PubMed2004

Enzymatic and oxidative metabolites of lycopene.

Using the post-mitochondrial fraction of rat intestinal mucosa, we have investigated lycopene metabolism. The incubation media was composed of NAD+, KCI, and DTT with or without added lipoxygenase. The addition of lipoxygenase into the incubation significantly increased the production of lycopene metabolites. The enzymatic incubation products of 2H10 lycopene were separated using high-performance liquid chromatography and analyzed by UV/Vis spectrophotometer and atmospheric pressure chemical ionization-mass spectroscopy. We have identified two types of products: cleavage products and oxidation products. The cleavage products are likely: (1) 3-keto-apo-13-lycopenone (C18H24O2 or 6,10,14-trimethyl-12-one-3,5,7,9,13-pentadecapentaen-2-one) with lambdamax = 365 nm and m/z =272 and (2) 3,4-dehydro-5,6-dihydro-15-apo-lycopenal (C20H28O or 3,7,11,15-tetramethyl-2,4,6,8,12,14-hexadecahexaen-l-al) with lambdamax= 380 nm and m/z = 284. The oxidative metabolites are likely: (3) 2-ene-5,8-lycopenal-furanoxide (C37H50O) with lambdamax = 415 nm, 435 nm, and 470 nm, and m/z = 510; (4) lycopene-5, 6, 5', 6'-diepoxide (C40H56O2) with lambdamax = 415 nm, 440 nm, and 470 nm, and m/z =568; (5) lycopene-5,8-furanoxide isomer (I) (C40H56O2) with lambdamax = 410 nm, 440 nm, and 470 nm, and m/z = 552; (6) lycopene-5,8-epoxide isomer (II) (C40H56O) with lambdamax = 410, 440, 470 nm, and m/z = 552; and (7) 3-keto-lycopene-5',8'-furanoxide (C40H54O2) with lambdamax = 400 nm, 420 nm, and 450 nm, and m/z = 566. These results demonstrate that both central and excentric cleavage of lycopene occurs in the rat intestinal mucosa in the presence of soy lipoxygenase.

Animals↗

PubMed2004

The effect of dietary glutathione and coenzyme Q10 on the prevention and treatment of inflammatory bowel disease in mice.

Because reactive oxygen species have been implicated as mediators of inflammatory bowel disease (IBD), we evaluated the potential preventive and therapeutic effects of two dietary antioxidants, glutathione (GSH) and coenzyme Q10 (CoQ10) on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty female 8-wk old Swiss-Webster mice were randomly assigned to 4 groups for a pre-treatment "prevention" study: (1) GSH (1% of diet); (2) CoQ10 (200 mg/kg/d); (3) DSS only (3% of drinking water); (4) control (no treatment). The mice in groups 1 and 2 were fed with GSH or CoQ10 for 21 wks, and the mice in groups 1, 2 and 3 were provided DSS from wk 7 for 4 cycles (1 cycle = 1 wk DSS followed by 2-wk water). Another 50 mice were randomly assigned to 4 groups for a 21-wk "treatment" study where the mice in groups 1, 2, and 3 were administered DSS for 6 cycles (18 wks) to induce colitis. GSH and CoQ10 were added from wk 7 until the completion of the protocol. Loose stools and hemocult positivity were modestly but significantly reduced with GSH or CoQ10 at several periods during the intervention in both the prevention and treatment studies. In contrast, histological evaluation revealed increases in colonic dysplasia and ulceration with GSH or CoQ10. Thus, in this mouse model, GSH and CoQ10 appear to have a beneficial effect on acute signs of IBD, but may have an adverse impact on the chronic pathophysiology of the disease. Further studies using additional animal models are required to determine whether GSH or CoQ10 provide a favorable or unfavorable benefit:risk ratio in the prevention or treatment of IBD.

Analysis of Variance↗

PubMed2004

beta-Carotene-vitamin A equivalence in Chinese adults assessed by an isotope dilution technique.

The present study was carried out to determine the conversion factor of synthetic (2)H-labelled beta-carotene to vitamin A in Chinese adults by using a stable-isotope dilution technique. Fifteen healthy volunteers aged 50-60 years were recruited for a 55 d experiment. The volunteers (nine males and six females) were each given a physiological dose of [(2)H8]beta-carotene (6 mg) in oil on the first day of the experiment, and a reference dose of [(2)H8]retinyl acetate (3 mg) in oil was given on the fourth day. Serum samples were collected at 0, 3, 5, 7, 9, 11, and 13 h on the first and the fourth days of the study, daily for 10 d, and then weekly from days 14 to 56. beta-Carotene and retinol were extracted from serum and isolated by HPLC, and their enrichments were respectively determined by using GC-electron capture negative chemical ionisation-MS and LC-atmospheric pressure chemical ionisation interface-MS. Four of the subjects exhibited beta-carotene to vitamin A conversion factors of >29.0:1 on a molar basis and were termed 'poor converters'. In the eleven normal converters (seven males and four females), the calculated conversion factors of beta-carotene to retinol ranged from 2.0:1 to 12.2:1 with an average of 4.8 (sd 2.8):1 on a molar basis, and from 3.8:1 to 22.8:1 with an average of 9.1 (sd 5.3):1 on a weight basis. The 52 d post-intestinal absorption conversion was estimated to be about 30 % of the total converted retinol.

Absorption↗

PubMed2004

Dietary vitamin A intakes of Filipino elders with adequate or low liver vitamin A concentrations as assessed by the deuterated-retinol-dilution method: implications for dietary requirements.

BACKGROUND: The vitamin A requirements of elderly humans have not been studied. OBJECTIVE: In a cross-sectional study of 60-88-y-old men (n = 31) and women (n = 31) in rural Philippines, we assessed the dietary intakes of elders with adequate (> or = 0.07 micromol/g) or low (< 0.07 micromol/g) liver vitamin A concentrations to estimate vitamin A requirements for this age group. DESIGN: Total-body vitamin A was assessed by the deuterated-retinol-dilution technique; liver vitamin A concentrations were assessed by assuming that liver weight is 2.4% of body weight and that, in this marginally nourished population, 70% of total-body vitamin A is in the liver; serum retinol was measured by HPLC; and dietary intakes were assessed with 3 nonconsecutive 24-h dietary recalls. The mean vitamin A intake + 2 SDs of subjects with adequate liver vitamin A concentrations was used to estimate an acceptable or sufficient vitamin A intake value for elders. RESULTS: The mean (+/- SD) vitamin A intakes of the men and women with adequate vitamin A in liver were 135 +/- 86 and 134 +/- 104 microg retinol activity equivalents (RAE)/d, respectively; intakes of the men and women with low vitamin A in liver were 75 +/- 53 and 60 +/- 27 microg RAE/d, respectively. Total-body vitamin A or liver vitamin A but not serum retinol correlated with dietary RAE, preformed vitamin A, beta-carotene, fat, and protein. An estimated acceptable or sufficient dietary vitamin A intake associated with adequate liver vitamin A concentrations in elders is 6.45 microg RAE/kg body wt; for a reference 76-kg man and a 61-kg woman, these values are approximately 500 and 400 microg RAE/d, respectively. CONCLUSION: The dietary vitamin A intakes of elders with adequate or low liver vitamin A concentrations as estimated by use of the deuterated-retinol-dilution technique are useful for assessing vitamin A requirements.

Aged↗

PubMed2004

Yogurt and gut function.

In recent years, numerous studies have been published on the health effects of yogurt and the bacterial cultures used in the production of yogurt. In the United States, these lactic acid-producing bacteria (LAB) include Lactobacillus and Streptococcus species. The benefits of yogurt and LAB on gastrointestinal health have been investigated in animal models and, occasionally, in human subjects. Some studies using yogurt, individual LAB species, or both showed promising health benefits for certain gastrointestinal conditions, including lactose intolerance, constipation, diarrheal diseases, colon cancer, inflammatory bowel disease, Helicobacter pylori infection, and allergies. Patients with any of these conditions could possibly benefit from the consumption of yogurt. The benefits of yogurt consumption to gastrointestinal function are most likely due to effects mediated through the gut microflora, bowel transit, and enhancement of gastrointestinal innate and adaptive immune responses. Although substantial evidence currently exists to support a beneficial effect of yogurt consumption on gastrointestinal health, there is inconsistency in reported results, which may be due to differences in the strains of LAB used, in routes of administration, or in investigational procedures or to the lack of objective definition of "gut health." Further well-designed, controlled human studies of adequate duration are needed to confirm or extend these findings.

Adult↗

PubMed2004

Use of the deuterated-retinol-dilution technique to monitor the vitamin A status of Nicaraguan schoolchildren 1 y after initiation of the Nicaraguan national program of sugar fortification with vitamin A.

BACKGROUND: Nicaragua initiated a national program of vitamin A fortification of its domestic sugar supply starting with the 1999-2000 sugarcane harvest. OBJECTIVE: This study was conducted to document any change in the vitamin A status of a cohort of children during the first year of the program. DESIGN: The vitamin A status of 21 Nicaraguan schoolchildren (mean age: 6.7 y; range: 5.3-9.3 y) was assessed in March 2000 and in March 2001. Total-body vitamin A stores and liver vitamin A concentrations were estimated with the deuterated-retinol-dilution (DRD) technique at a dose of 5 mg [(2)H(4)]retinyl acetate at baseline and 5 mg [(2)H(8)]retinyl acetate during the repeat test 1 y later. Plasma retinol and carotenoids were measured by HPLC. RESULTS: Median total-body vitamin A stores increased from 0.33 to 0.72 mmol (P = 0.0001), liver vitamin A concentrations from 0.52 to 0.78 mumol/g (P = 0.0003), and plasma retinol concentrations increased from 0.97 to 1.17 mumol/L (P = 0.01). CONCLUSION: The vitamin A status of Nicaraguan schoolchildren improved during the year after the initial distribution of vitamin A-fortified sugar in Nicaragua.

Body Height↗

PubMed2004

The enigma of beta-carotene in carcinogenesis: what can be learned from animal studies.

Beta-carotene and other carotenoids have been thought to have anti-cancer activity, either because of antioxidant activity or because of their ability to be converted to vitamin A. Nevertheless, two large scale intervention studies in humans using high doses of beta-carotene found that beta-carotene supplementation resulted in more lung cancer rather than less lung cancer among smoking and asbestos exposed populations. Studies conducted in the ferret have elucidated molecular mechanisms behind this observation, in that high-dose beta-carotene and smoke exposure in these animals leads to squamous metaplasia, a pre-cancerous lesion in the lung. High dose beta-carotene in the smoke exposed animals was found to give rise to a number of transient oxidative metabolites, which include P450 enzymes that result in the destruction of retinoic acid, and diminished retinoid signaling, and enhanced cell proliferation. In addition, eccentric cleavage beta-carotene metabolites facilitate the binding of smoke derived carcinogens to DNA. In other ferret studies low dose beta-carotene smoke exposure provided mild protection against squamous metaplasia. Thus, it appears that the explanation of the apparent paradoxical effects of beta-carotene on lung cancer is related to dose. The metabolism and breakdown of natural products should be thoroughly investigated in animal models before embarking on large scale intervention trials, particularly when using unusually high doses that greatly exceed normal dietary levels.

Animals↗

PubMed2004

Low dose beta-carotene supplementation of ferrets attenuates smoke-induced lung phosphorylation of JNK, p38 MAPK, and p53 proteins.

We demonstrated previously that smoke exposure and/or high-dose beta-carotene supplementation decreases levels of retinoic acid and retinoic acid receptor beta (RARbeta) protein, but increase levels of c-Jun and proliferating cellular nuclear antigen protein in the lungs of ferrets. In contrast, low-dose beta-carotene can prevent the decreased lung retinoic acid and the smoke-induced lung lesions. In the present study, we investigated whether smoke exposure and/or beta-carotene supplementation could affect Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and p53 in the lungs of ferrets. Ferrets were subjected to cigarette smoke exposure and either a high or low dose of beta-carotene (2 x 3 factorial design) for 6 mo. There were greater protein levels of phosphorylated JNK, p38, and c-Jun, but lower levels of MAPK phophatase-1 (MKP-1) in groups exposed to smoke and/or high dose beta-carotene. Both phosphorylated-p53 and total p53 were substantially increased in the lungs of these groups. In contrast, low-dose beta-carotene greatly attenuated the smoke-induced phosphorylation of JNK, p38, c-Jun, p53, and total p53, accompanied by upregulated MKP-1. Smoke exposure increased MAPK kinase-4 (MKK4) phosphorylation regardless of beta-carotene supplementation. These data indicate that restoration of retinoic acid and MKP-1 by low-dose beta-carotene in the lungs of ferrets may prevent the smoke-induced activation of the JNK-dependent signaling pathway, p38 MAPK, and the associated phosphorylation of p53, thereby lowering the risk of the smoke-related lung lesions. These data provide supportive evidence that the beneficial vs. detrimental effects of beta-carotene supplementation are related to the dosage of beta-carotene administered.

Animals↗