Diet adherence dynamics and physiological responses to a tomato product whole-food intervention in African-American men.

Tomatoes may have beneficial effects on prostate health. Efficacy trials would require long-term adherence to high levels of tomato product (TP) consumption. Therefore, factors that affect adherence in men most at risk and whether increased consumption of TP negatively affects diet and health are important concerns. Cancer-free African­American (AA) men (n 36) with mean serum prostate-specific antigen of 7.4 SD 5.6) ng/ml were randomised to consume one serving of TP/d or a control diet for 3 months. Mean intervention group lycopene intake rose to 464%, with negligible control group increase. Plasma lycopene levels rose by 53 and 40% in the intervention group in months 1 and 3, respectively (P < 0.0001), with no control group change. The intervention group's barriers to adherence score was inversely associated with both dietary (r -0.49, P = 0.02) and plasma lycopene concentration (r -0.37, P = 0.02). Their TP disadvantage score negatively correlated with the 3-month plasma lycopene concentrations (r -0.37, P = 0.008) and their weekly incentives and impediments were remarkably stable, 'concern for prostate health' being the most consistent over time. 'Liking tomatoes' and 'study participation' decreased in citation frequency at weeks 6 and 9, respectively. No major shifts occurred in dietary cholesterol or saturated fat, with no adverse effects on gastrointestinal complaints, serum total cholesterol, body weight or blood pressure. Lower socio-economic status AA men at higher prostate cancer risk can successfully achieve a whole food intervention goal with a corresponding rise in plasma lycopene concentrations, with no adverse effects on self-selected diet quality or health parameters.

National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline.

The National Institute on Aging and the Office of Medical Applications of Research of the National Institutes of Health convened a State-of-the-Science Conference on 26-28 April 2010 to assess the available scientific evidence on prevention of cognitive decline and Alzheimer disease. This article provides the panel's assessment of the available evidence.

Exfoliated buccal mucosa cells as a source of DNA to study oxidative stress.

The extent of oxidative DNA damage is considered a biomarker of carcinogenic process and could be investigated in population studies using easily obtained cells. The oxidized DNA base adduct 8-hydroxy-2-deoxyguanosine (8-OHdG) released by enzymatic hydrolysis of DNA is commonly assayed by high performance liquid chromatography with electrochemical detection. It is expressed as a ratio of 8-OHdG to unoxidized deoxyguanosine. We modified and improved this method, determined the optimal time for harvesting buccal mucosa cells (BMC), assessed whether they mirror peripheral circulating blood cell DNA damage, and compared the anticoagulants, heparin, and EDTA for consistency in measurement of leukocyte 8-OHdG. Thirty-one healthy participants, randomized into two groups, donated BMC and blood samples. Samples were collected at baseline and either 3 or 7 days after baseline. Results showed no correlation between 8-OHdG/deoxyguanosine ratios in BMC and peripheral blood leukocytes at any time point regardless of harvest time. BMC had much higher oxidative DNA damage, but displayed a 25.6% reduction in the oxidized DNA adduct level (P < 0.04) at 3 days after baseline. Leukocytes collected in heparin and EDTA had similar 8OHdG/deoxyguanosine ratios; however, EDTA was preferred, as it produced a clean nuclear pellet without hemoglobin contamination, and the results were less variable. This improved assay shows within subject stability over time in both leukocyte and BMC DNA damage, increasing the probability that small intervention differences can be detected in healthy subjects. Buccal cells provide an accessible pool of epithelial cells that represents higher levels of DNA damage than circulating leukocytes.

Correlations of dietary patterns with prostate health.

Both genetic and environmental influences may be involved in etiology of prostate health and prostate cancer. These include ethnic origin, family history, smoking, and diet. Adiposity and excess energy intake are potentially distinct risk factors and positive associations with prostate cancer risk for both were observed among case-control and cohort studies. Some epidemiological studies support an association between dietary fat, particularly saturated or animal fats, and prostate cancer risk. Of these, several suggest reduced risk with low-fat diets high in n-3 fatty acids and increased risk with high-fat diets rich in n-6 fatty acids. Others suggested association with higher meat intake, possibly due to heterocyclic amines and polycyclic aromatic hydrocarbons, produced during grilling or frying. Positive association of prostate cancer risk with dairy intake could involve alpha-methylacyl-CoA racemase activity (required for beta-oxidation of phytanic acid present in dairy products and red meat) or the suppression of vitamin D activity by calcium. Inverse associations were observed with dietary intake of plant foods. These include cereals, soy products, and fruit and vegetable sources of carotenoids. Numerous plant constituents may act synergistically in the prevention and inhibition of prostate disorders. These diet-risk associations may lead to future individualized diet recommendations based upon genetic polymorphisms.

Role of Commodity Boards in Advancing the Understanding of the Health Benefits of Whole Foods: California Dried Plums.

Food and agriculture commodity boards have become important funders of nutrition research. There are benefits and cautions (biases toward health benefits, failure to publish negative results, and aggressive promotion of single studies) for this activity. The California Dried Plum Board, along with other commodity boards, have developed independent Scientific Nutrition Advisory Panels to guide and evaluate the research they fund. In the case of the California Dried Plum Board, this has resulted in research that has distinguished the nature and dose of dried plum and juice to maintain bowel health and opened up a surprising new function for dried plum in the prevention of age-related bone loss.

Role of lycopene and tomato products in prostate health.

Epidemiological evidence associating the decreased risk of prostate cancer with frequent consumption of tomato products inspired us to conduct a small intervention trial among patients diagnosed with prostate adenocarcinoma. Tomato sauce pasta was consumed daily for 3 weeks before their scheduled prostatectomy, and biomarkers of tomato intake, prostate cancer progression and oxidative DNA damage were followed in blood and the available prostate tissue. The whole food intervention was so well accepted by the subjects that the blood lycopene (the primary carotenoid in tomatoes responsible for their red color) doubled and the prostate lycopene concentration tripled during this short period. Oxidative DNA damage in leukocytes and prostate tissues was significantly diminished, the latter mainly in the tumor cell nuclei, possibly due to the antioxidant properties of lycopene. Quite surprising was the decrease in blood prostate-specific antigen, which was explained by the increase in apoptotic death of prostate cells, especially in carcinoma regions. Prostate cancer cell cultures (LNCaP) were also sensitive to lycopene in growth medium, which caused an increased apoptosis and arrested the cell cycle. A possible explanation of these promising results may reside in lycopene effects on the genes governing the androgen stimulation of prostate growth, cytokines and on the enzymes producing reactive oxygen species, all of which were recently discovered by nutrigenomic techniques. Other phytochemicals in tomato may act in synergy with lycopene to potentiate protective effects and to help in the maintenance of prostate health.

Effects of tomato paste extracts on cell proliferation, cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells.

Since tomato consumption is associated with decreased risk of prostate cancer, cell proliferation, cell cycle progression and apoptosis by LNCaP human prostate cancer cells might elucidate action of tomatoes. To discover possible bioactive fractions of tomatoes, whole tomato paste and its water and hexane extract were used and biomarkers of carcinogenesis were measured. After 6, 24 and 48 hr of incubation, cells were harvested and determined cell growth. Tomato paste hexane extract inhibited cell proliferation by 33% compared to the control after 48 hr incubation. Whole tomato paste and its water extract showed only modest growth inhibition. Tomato paste hexane extract at 5 microM lycopene increased G2/M-phase of the cell cycle from 13 to 28% and decreased S-phase cells from 45 to 29%. Apoptosis was observed at the 5 microM hexane extract at the late stages during 24 and 48 hr treatment. Tomato, therefore, deserves study as a potential chemopreventive/chemotherapeutic agent.

Effects of lycopene and tomato paste extracts on DNA and lipid oxidation in LNCaP human prostate cancer cells.

Animal and epidemiological studies point to a cancer preventive/therapeutic role for tomato products and its antioxidant, lycopene. It is hypothesized that lycopene will behave as an antioxidant at low concentrations and as a prooxidant at high concentrations in LNCaP human prostate cancer cell culture systems. We characterized the antioxidant, and prooxidant effects of a hexane extract of tomato paste (TP) and water solubilized lycopene at different concentrations using a prostate cancer cell line. Placebo (5% triglyceride, Roche Inc.) was used as a control. After 6, 24 hr and 48 hr incubation, LNCaP cells were harvested and used for each measurement. Cellular proliferation was determined using the MTT colorimetric assay. Lycopene and TP hexane extract inhibited cell growth in a dose-dependent (0.1-50 microM lycopene) manner and growth inhibition was 55% and 35% at 1 microM lycopene and TP hexane extract, respectively after 48 hr incubation. The levels of 8-hydroxydeoxyguanosine/deoxyguanosine (an oxidative DNA damage product) was significantly increased starting at 5 microM lycopene from both TP hexane extract and pure lycopene after 24 and 48 hr incubation with no protection at the lower concentrations. Malondialdehyde formation (a lipid peroxidation product measured by HPLC separation of the MDA-TBA adduct) was significantly reduced at low concentrations (0.1-1 microM) of lycopene in all treatments. Clinically relevant concentrations of lycopene and the tomato fraction containing lycopene significantly reduced LNCaP cancer cell survival which can only be partially explained by increased DNA damage at high lycopene concentrations (> 5 microM). Low concentrations of lycopene acted as a lipid antioxidant but did not protect DNA.

Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects.

This report details the findings of a single-dose Phase I pharmacokinetic and toxicity study of a food-based formulation of lycopene in healthy adult male subjects. Five dosing groups (n = 5 per group) were sequentially treated with increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were collected for a total of 28 days (672 h) after administration of single doses of lycopene. The mean time (t(max)) to reach maximum total lycopene concentration (C(max)) ranged from 15.6 to 32.6 h. The C(max) for total lycopene ranged between 4.03 and 11.27 microg/dl (0.075-0.210 microm). Mean AUC(0-96) and elimination half-life for total lycopene ranged from 214 to 655 microg h/dl (3.986-12.201 micromol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene exposure parameters (e.g., C(max) and AUC(0-96)) were not proportional to increments in dose, with larger increases observed at the lowest end of the dosing range (10-30 mg). Chylomicron lycopene was measured during the first 12 h with the differences observed among the dosing groups not reaching statistical significance. These findings may reflect a process of absorption that is saturable at very low dosing levels or may be explained by the large interindividual variability in attained lycopene concentrations that were observed within each dosing group. Pharmacokinetic parameters for trans- and cis-lycopene isomers were calculated and are reported here. The formulation was well tolerated with minimal side effects, which were mainly of gastrointestinal nature and of very low grade.

Can the consumption of tomatoes or lycopene reduce cancer risk?

Lycopene, a natural antioxidant found predominantly in tomato products, is attracting attention as a cancer prevention agent. Serum and dietary lycopene levels have been found to be inversely related to the incidence of several types of cancer, including prostate cancer. Although the antioxidant properties of lycopene are thought to be primarily responsible for its apparent beneficial effects, other mechanisms may also be involved. We outline the possible mechanisms of action of lycopene and review the current findings of in vitro and in vivo studies in cancer prevention and to some extent treatment. We examine the epidemiologic evidence regarding consumption of tomato and tomato products with the risk of cancer at various sites. Data suggest lycopene may account for or contribute to chemoprevention, but this hypothesis requires further study. Numerous other potentially beneficial compounds are present in tomatoes and complex interactions among multiple components may contribute to the anticancer properties of tomatoes.

A longitudinal evaluation of oxidative stress in trauma patients.

BACKGROUND: The purpose of this study was to determine the course of oxidative stress in trauma patients as measured by antioxidant disappearance and modulation of DNA damage. The study also explored the role of injury severity and the effect of changes in plasma lipoprotein concentration as the result of hemodilution on lipid-soluble plasma antioxidant concentrations. METHODS: The study population included 17 adult male trauma patients in an urban level-1 trauma hospital and 12 healthy adult male controls. Blood was collected immediately after admission in the emergency room, and on days 2, 3, 4, 6, and 8 of admission. Plasma antioxidant concentrations and total cholesterol concentrations were evaluated. DNA damage was evaluated using the ratio of 8-hydroxydeoxyguanosine to deoxyguanosine (8OhdG to dG). Admission data were compared with data from controls. RESULTS: Plasma antioxidant concentrations (except alpha-tocopherol) significantly decreased by 9.9% to 34.3% in the 24 hours after trauma and remained depressed throughout day 8. Repeated measures regression analysis for trend showed a significant increase in unadjusted alpha-tocopherol from day 1 to day 8 (p < .008). No other unadjusted antioxidant or plasma cholesterol showed a significant change. After individually adjusting antioxidant concentrations by total cholesterol, only gamma-tocopherol (22.2%) and lycopene (22.6%) were decreased (p < .04) in the 24 hours after trauma. Repeated measures regression analysis for trend for the cholesterol-adjusted antioxidants showed a significant decrease from day 1 to day 8 for cholesterol-adjusted alpha-carotene (p < .007) and beta-carotene (p < .007). Trauma patients were divided into more and less severely injured groups based on Injury Severity Score (ISS). Decreases in antioxidant concentration from day 1 to day 2 were found for the patients in the more injured group, with no significant differences from day 1 to day 2 in the less severely injured group. Cholesterol-adjusted gamma-to copherol (29.7%, p < .003) and lycopene (32.7%, p < .05) decreased from day 1 to day 2 in the more severely injured group. Using repeated measures regression analysis for trend, the only antioxidant that was significantly different in the high versus low ISS groups from day 1 through day 6 was cholesterol-adjusted lutein-zeaxanthin (p < .02). Compared with controls, trauma patients had significantly lower (27.3% to 64.9%) concentrations of all cholesterol-adjusted antioxidants at day 1 except for lycopene. Trauma patients had higher leukocyte 8OhdG to dG ratios at admission (42.6%, p < .05), but 8OhdG to dG ratios tended to decrease over the 24 hours after trauma (p < .07). This decrease was greater in the 3 trauma patients with an admission 8OhdG to dG ratio greater than 6 x 10(-5) (59.3% versus 0.05%, p < .03). CONCLUSIONS: The difference in antioxidant concentrations between trauma patients and controls may have been associated with oxidative stress or with a poorer diet. The difference between antioxidant concentrations and cholesterol-adjusted antioxidant concentrations is likely caused by hemodilution or by changes in plasma lipid levels as a result of trauma. Therefore, individually adjusting lipid-soluble antioxidant concentrations by total cholesterol concentrations is important in trauma patients. Leukocyte 8OhdG to dG ratios were already elevated in trauma patients on admission but returned nearly to control levels 24 hours later, indicating short-term responsiveness to DNA oxidation in trauma patients and an extensive capacity for DNA repair within 24 hours.

Liquid chromatography-mass spectrometry of cis- and all-trans-lycopene in human serum and prostate tissue after dietary supplementation with tomato sauce.

Several epidemiological studies suggest a lower incidence of prostate cancer in men who routinely consume tomato products. Tomatoes are the primary dietary source of lycopene, which is among the most potent antioxidants of the carotenoids. Men with clinical stage T1 or T2 prostate adenocarcinoma were recruited (n = 32) and consumed tomato sauce based pasta dishes for 3 weeks (equivalent to 30 mg of lycopene per day) before radical prostectomy. Prostate tissue from needle biopsy just before intervention and prostectomy after supplementation from a subset of 11 subjects was evaluated for both total lycopene and lycopene geometrical isomer ratios. A gradient HPLC system using a C(18) column with UV-vis absorbance detection was used to measure total lycopene. Because the absorbance detector was insufficiently sensitive, HPLC with a C(30) column and positive ion atmospheric pressure chemical ionization mass spectrometric (LC-MS) detection was developed as a new assay to measure the ratio of lycopene cis/trans isomers in these samples. The limit of detection of the LC-MS method was determined to be 0.93 pmol of lycopene on-column, and a linear response was obtained over 3 orders of magnitude. Total lycopene in serum increased 2.0-fold from 35.6 to 69.9 microg/dL (from 0.664 to 1.30 microM) as a result of dietary supplementation with tomato sauce, whereas total lycopene in prostate tissue increased 3.0-fold from 0.196 to 0.582 ng/mg of tissue (from 0.365 to 1.09 pmol/mg). all-trans-Lycopene and at least 14 cis-isomer peaks were detected in prostate tissue and serum. The mean proportion of all-trans-lycopene in prostate tissue was approximately 12.4% of total lycopene before supplementation but increased to 22.7% after dietary intervention with tomato sauce. In serum there was only a 2.8% but statistically significant increase in the proportion of all-trans-lycopene after intervention. These results indicate that short-term supplementation with tomato sauce containing primarily all-trans-lycopene (83% of total lycopene) results in substantial increases in total lycopene in serum and prostate and a substantial increase in all-trans-lycopene in prostate but relatively less in serum.

Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells.

Lycopene is one of the major carotenoids and is found almost exclusively in tomatoes and tomato products. Since tomato consumption is associated with decreased risk of prostate cancer, characterizing the effects of lycopene on cell growth or survival, cell cycle progression, and apoptosis in LCNaP human prostate cancer cells might elucidate the mechanisms of actions of lycopene. To discover the possible anti-cancer mechanism of lycopene, water-soluble lycopene was used, and cell cycle arrest and apoptosis were measured. Placebo formulation at each lycopene dose at 0.1, 1, and 5 microM was used as a control. After 6, 24, and 48 hours of incubation, cells were harvested and measured for cell viability. Lycopene at 1 microM inhibited cell growth by 31%, compared with its placebo formulation after a 48-hour incubation. Lycopene at 5 microM increased the number of cells in the G(2)/M phase of the cell cycle from 13% to 28% and decreased S-phase cells from 45% to 29%, while no shifts in cell cycle were detected in placebo-treated groups. Apoptosis was observed at the 5 microM lycopene formulation at the late stages during the 24- and 48-hour treatments. Lycopene, therefore, deserves further study as a potential chemopreventive/chemotherapeutic agent.

Effects of heat treatment on the carotenoid and tocopherol composition of tomato.

The objective of this study was to determine the influence of thermal processing on the assessment of tocopherols and carotenoids, as well as their isomer formation in tomatoes. The sliced tomatoes were heated in an oven at 100, 130, and 160 °C for 5, 10, and 20 min, then freeze-dried. Freeze-dried samples were finely ground and the analysis was performed on lyophilized samples. The average concentrations of total lycopene, lutein, ß-carotene, α-tocopherol, and γ-tocopherol in fresh tomatoes (in 100 g dry weight) were 21.2, 1.1, 2.7, 8.0, and 2.5 mg, respectively. Oven baking of tomato at 160 °C for 20 min led to a significant increase in the apparent measurement of lycopene, ß-carotene, and α-tocopherol content by 75%, 81%, and 32%, respectively. Heating induced isomerization of (all-E) to various (Z) isomers of lycopene, and we found that the total (Z)-lycopene proportion in the tomatoes increased with longer heating time. (All-E)-lycopene constituted 75.4% in fresh tomatoes and decreased to 52.5% in oven-baked tomatoes (160 °C, 20 min), while (5Z)-lycopene increased from 9.4% to 17.9% of total lycopene. However, ß-carotene release and isomerization was less influenced by the heat treatment than that of lycopene. These results suggested that thermal processes might break down cell walls and enhance the release of carotenoids and tocopherols from the matrix, as well as increase isomerization of lycopene and ß-carotene.

Antioxidant effects of lycopene in African American men with prostate cancer or benign prostate hyperplasia: a randomized, controlled trial.

Consumption of tomato products is associated with a decreased risk of developing prostate cancer, and lycopene, the red carotenoid in the tomato, is a potent antioxidant that might contribute to this chemoprevention activity. A double-blind, randomized, placebo-controlled trial of 105 African American men veterans, recommended for prostate biopsy to detect cancer, was carried out to investigate whether oral administration of lycopene increases lycopene levels in blood and prostate tissue and lowers markers of oxidative stress. Urology patients were randomly assigned to receive 30 mg/d of lycopene as a tomato oleoresin or placebo for 21 days prior to prostate biopsy for possible diagnosis of prostate cancer. A total of 47 men had a diagnosis of prostate cancer, and 58 men had a diagnosis of benign prostate hyperplasia. Diet, smoking, and drinking habits were assessed. For the men receiving lycopene, the mean lycopene concentration increased from 0.74 ± 0.39 to 1.43 ± 0.61 µmol/L in plasma (P < 0.0001) and from 0.45 ± 0.53 to 0.59 ± 0.47 pmol/mg in prostate tissue (P = 0.005). No significant changes in the DNA oxidation product 8-oxo-deoxyguanosine and the lipid peroxidation product malondialdehyde were observed in prostate tissue and plasma, respectively, as a result of lycopene administration.

Risk factors and preventive interventions for Alzheimer disease: state of the science.

BACKGROUND: Numerous studies have investigated risk factors for Alzheimer disease (AD). However, at a recent National Institutes of Health State-of-the-Science Conference, an independent panel found insufficient evidence to support the association of any modifiable factor with risk of cognitive decline or AD. OBJECTIVE: To present key findings for selected factors and AD risk that led the panel to their conclusion. DATA SOURCES: An evidence report was commissioned by the Agency for Healthcare Research and Quality. It included English-language publications in MEDLINE and the Cochrane Database of Systematic Reviews from 1984 through October 27, 2009. Expert presentations and public discussions were considered. STUDY SELECTION: Study inclusion criteria for the evidence report were participants aged 50 years and older from general populations in developed countries; minimum sample sizes of 300 for cohort studies and 50 for randomized controlled trials; at least 2 years between exposure and outcome assessment; and use of well-accepted diagnostic criteria for AD. DATA EXTRACTION: Included studies were evaluated for eligibility and data were abstracted. Quality of overall evidence for each factor was summarized as low, moderate, or high. DATA SYNTHESIS: Diabetes mellitus, hyperlipidemia in midlife, and current tobacco use were associated with increased risk of AD, and Mediterranean-type diet, folic acid intake, low or moderate alcohol intake, cognitive activities, and physical activity were associated with decreased risk. The quality of evidence was low for all of these associations. CONCLUSION: Currently, insufficient evidence exists to draw firm conclusions on the association of any modifiable factors with risk of AD.

NIH state-of-the-science conference statement: Preventing Alzheimer's disease and cognitive decline.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on prevention of Alzheimer's disease and cognitive decline. PARTICIPANTS: A non-Department of Health and Human Services, nonadvocate 15-member panel representing the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, family caregiving, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the Duke University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: Cognitive decline and Alzheimer's disease are major causes of morbidity and mortality worldwide and are substantially burdensome to the affected persons, their caregivers, and society in general. Extensive research over the past 20 years has provided important insights on the nature of Alzheimer's disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. Currently, firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer's disease. Highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer's disease are lacking, and available criteria have not been uniformly applied. Evidence is insufficient to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer's disease. We recognize that a large amount of promising research is under way; these efforts need to be increased and added to by new understandings and innovations (as noted in our recommendations for future research). For example, ongoing studies including (but not limited to) studies on antihypertensive medications, omega-3 fatty acids, physical activity, and cognitive engagement may provide new insights into the prevention or delay of cognitive decline or Alzheimer's disease. This important research needs to be supplemented by further studies. Large-scale population-based studies and randomized controlled trials (RCTs) are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer's disease among persons at risk, and to identify factors that may slow the progression of Alzheimer's disease among persons in whom the condition is already diagnosed.

DNA damage, a biomarker of carcinogenesis: its measurement and modulation by diet and environment.

Free radicals and other reactive oxygen or nitrogen species are constantly generated in vivo and can cause oxidative damage to DNA. This damage has been implicated to be important in many diseases, including cancer. The assessment of damage in various biological matrices, such as tissues, cells, and urine, is vital to understanding this role and subsequently devising intervention strategies. During the last 20 years, many analytical techniques have been developed to monitor oxidative DNA base damage. High-performance liquid chromatography-electrochemical detection and gas chromatography-mass spectrometry are the two pioneering contributions to the field. Currently, the arsenal of methods available include the promising high-performance liquid chromatography-tandem mass spectrometry technique, capillary electrophoresis, 32P-postlabeling, antibody-base immunoassays, and assays involving the use of DNA repair glycosylases such as the comet assay. The objective of this review is to discuss the biological significance of oxidative DNA damage, evaluate the effectiveness of several techniques for measurement of oxidative DNA damage in various biological samples and review current research on factors (dietary and non-dietary) that influence DNA oxidative damage using these techniques.

Postprandial lipid oxidation and cardiovascular disease risk.

A mild pro-oxidative state accompanies meal ingestion, which results in an increase in biomarkers of inflammation, adhesion, and endothelial dysfunction, all of which are factors in the development of cardiovascular disease. Both fat and carbohydrate can cause the effect, which is additive and exacerbated by diabetes. The presence of lipid, glucose, and cholesterol oxidation products of dietary or endogenous origin may contribute to postprandial oxidative stress. However, the generation of excess superoxide due to abundant energy substrate after the meal may be a predominate factor resulting in oxidative stress and a decrease in nitric oxide, which is important to endothelial function. Remediation of postprandial oxidative stress through direct reduction of superoxide generation and simultaneous consumption of antioxidants with each meal should be a focus of future research.

Esterification does not impair lutein bioavailability in humans.

Age-related macular degeneration (ARMD) is inversely associated with the accumulation of lutein + zeaxanthin in the macula, but higher lutein intakes are inconsistently related to reduced risk of ARMD in epidemiologic studies. Resolution of efficacy awaits clinical trials designed with knowledge of lutein supplement pharmacokinetics. Lutein bioavailability was determined for lutein diester and unesterified lutein formulations as they might be incorporated into dietary supplements. Healthy subjects (n = 18) consumed a single dose of each formulation (either 0.5 or 0.67 micro mol lutein/kg body, 10 and 8 subjects, respectively) in random order, and the appearance of free lutein + zeaxanthin was measured in serum from 0 to 408 h. Areas under the serum concentration x time curves (AUC), as a measure of bioavailability, were independent of gender, body mass index and lutein dose. The lutein diester formulation was 61.6% more bioavailable than the unesterified lutein formulation with higher mean AUC, maximum serum concentration and ascending slope (P < 0.05). The AUC was greater in 14 of 18 subjects when they consumed the lutein diester formulation. Comparison with data from previous studies suggested that dissolution was a greater limitation to bioavailability than lutein ester hydrolysis because an oil-solubilized unesterified lutein preparation, given at 0.5 micro mol/kg body, resulted in greater mean peak concentrations and AUC compared with either the unesterified or lutein diester formulations used in our study. In conclusion, the lutein diester formulation poses no impediment to lutein bioavailability at the doses tested, but formulation dissolution is an important factor in lutein bioavailability and should be evaluated before a supplement and dose are selected for use in clinical trials.