beta-carotene and Alzheimer-Disease

Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer's disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD.. Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis.. Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger's test.. Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = -0.86, 95% CI: -1.67 to -0.05, p = 0.04) and zeaxanthin (SMD = -0.59; 95% CI: -1.12 to -0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95% CI: -0.68 to 0.26, p = 0.39), β-carotene (SMD = 0.04, 95% CI: -0.57 to 0.65, p = 0.9), lycopene (SMD = -0.12, 95% CI: -0.96 to 0.72, p = 0.78), and β-cryptoxanthin (SMD = -0.09, 95% CI: -0.83 to 0.65, p = 0.81) did not achieve significant differences.. Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.

Topics: Alzheimer Disease; beta Carotene; Biomarkers; Carotenoids; Case-Control Studies; Humans; Lycopene; Zeaxanthins

To systematically evaluate the levels of vitamin C, vitamin E and β-carotene in the plasma of Alzheimer's disease( AD) patients.. In this study, literature of the levels of vitamin C, vitamin E and β-carotene in the plasma of AD patients were collected by retrieving the database of Pub Med, Science Direct, CNKI and Wan Fang( from they were built to July 2017).. Meta-analysis result showed that, compared with the control group, the level of vitamin E in the plasma of AD patients declined significantly( SMD =-1. 49 μmol/L, 95% CI-2. 08--0. 89 μmol/L, P <0. 001). However, no differences were determined in the levels of the plasma vitamin C and β-carotene between the two groups( vitamin C: SMD =-1. 43 μmol/L, 95% CI-3. 05-0. 19 μmol/L, P = 0. 083; β-carotene: SMD =-0. 61 μmol/L, 95% CI-1. 40-0. 18 μmol/L, P = 0. 131).. Increasing vitamin E level in the plasma through vitamin E riched diet may be useful to prevent AD. However it is not yet believed the benefical role on AD to increase vitamin C and β-carotene.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Ascorbic Acid; beta Carotene; Female; Humans; Male; Reference Values; Vitamin E

Topics: Alzheimer Disease; Animals; Antioxidants; Apoptosis; beta Carotene; Carotenoids; Humans; Metabolic Diseases; Neoplasms; Reactive Oxygen Species; Receptors, Cytoplasmic and Nuclear; Retinoids; Tretinoin; Vitamin A

In view of the vital role of oxidative stress in the pathogenesis of Alzheimer's disease (AD), the potential of antioxidant supplements to prevent AD have gained much interest, while there are conflicting results on this topic in recent years. The purpose of the present study is to comprehensively evaluate the association between dietary intakes, instead of supplements, of the most common three antioxidants (vitamin E, vitamin C, and β-carotene) and the risk of AD on the basis of the meta-analysis studies published up to October 2011 in Medline and Scopus databases. In total, seven articles were included in the meta-analysis. According to the pooled relative risk [(95% CI) 0.76 (0.67-0.84) for vitamin E, 0.83 (0.72-0.94) for vitamin C, and 0.88 (0.73-1.03) for β-carotene], dietary intakes of the three antioxidants can lower the risk of AD, with vitamin E exhibiting the most pronounced protective effects. The findings will be of significance to the prevention and interventional treatment of AD.

Topics: Alzheimer Disease; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Oxidative Stress; Risk Factors; Vitamin E

The wave of individuals impacted by dementia continues to rise rapidly as worldwide lifespan increases. Dietary strategies to slow cognitive decline and prolong time to clinical dementia remain understudied, but with potentially powerful public health consequences. Indeed, previously conducted large, randomized, placebo-controlled trials of micronutrients remain an under-leveraged resource to study changes in cognitive performance. As a motivating example, we highlight an ancillary report from the Physicians' Health Study, where subjects randomized to β-carotene (a provitamin A carotenoid) had a more attenuated change in longitudinal global cognitive performance and verbal memory, as compared to subjects randomized to placebo. Despite mechanistic evidence from cell and animal studies supporting a vitamin A-mediated role in the biology associated with cognition, limited follow-up work has been conducted. We argue that dietary factors (including provitamin A) deserve a second look, leveraging multi-omic approaches, to elucidate how they may mitigate cognitive decline and dementia risk.

Topics: Alzheimer Disease; beta Carotene; Cognition; Cognitive Dysfunction; Dementia; Humans; Provitamins

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

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; beta Carotene; Biomarkers; Female; Humans; Male; Multivariate Analysis; Peptide Fragments; tau Proteins

To elucidate the possible role of carotenoids and vitamin A as risk factors for Alzheimer's disease (AD), we compared serum levels of beta-carotene and alpha-carotene, and vitamin A, measured by isocratic high performance liquid chromatography, of 38 AD patients and 42 controls. The serum levels of alpha-carotene did not differ significantly between AD patients and control groups. However, the serum levels of beta-carotene and vitamin A were significantly lower in the AD-patient group. These values did not correlate to age, age at onset or score on the MiniMental State Examination. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that low serum beta-carotene concentrations in AD patients could be related to a deficiency in dietary intake of this provitamin, although its possible relationship with risk for AD could not be excluded.

Topics: Aged; Alzheimer Disease; Antioxidants; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Female; Humans; Male; Reference Values; Risk Factors; Vitamin A

This study aims to examine the relationships of dietary α-carotene and β-carotene intake with cognitive function. The data were selected from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. A total of 2009 participants were included in this analysis. Dietary α-carotene and β-carotene intake were averaged by two 24-h dietary recalls. The Consortium to Establish a Registry for Alzheimer's Disease Word Learning subset (CERAD W-L), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST) were used to evaluate cognitive function. Logistic regression and restricted cubic spline models were applied to explore the associations of dietary α-carotene and β-carotene intake with cognitive performance. After adjusting for all confounding factors, compared with individuals in the lowest quartile of β-carotene dietary intake, those in the highest quartile had lower risks of both CERAD W-L decline [odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.44-0.90] and AFT decline (OR = 0.66, 95% CI: 0.47-0.94). In addition, the third quartile of β-carotene dietary intake had a significantly decreased risk of lower DSST (OR = 0.67, 95% CI: 0.48-0.83). Compared with the lowest quartile of α-carotene intake, the OR of AFT decline in the highest intake quartile was 0.66 (95% CI: 0.46, 0.94). For males, both dietary α-carotene and β-carotene intake were associated with a decreased risk of AFT decline (OR = 0.42, 95% CI: 0.25-0.71; OR = 0.51, 95% CI: 0.30-0.85, respectively). For females, dietary α-carotene intake was associated with a decreased risk of CERAD W-L decline (OR = 0.55, 95% CI: 0.33-0.91) and dietary β-carotene intake was associated with decreased risks of both CERAD W-L and AFT decline (OR = 0.37, 95% CI: 0.21-0.64; OR = 0.58, 95% CI: 0.37-0.91, respectively). Our results suggested that higher dietary α-carotene and β-carotene intake had inverse effects on cognitive function decline among older adults.

Topics: Alzheimer Disease; Animals; beta Carotene; Cognition; Cross-Sectional Studies; Female; Male; Nutrition Surveys

The aggregation of amyloid beta (Aβ) into fibrillar aggregates is a key feature of Alzheimer's disease (AD) pathology. β-carotene and related compounds have been shown to associate with amyloid aggregates and have direct impact on the formation of amyloid fibrils. However, the precise effect of β-carotene on the structure of amyloid aggregates is not known, which poses a limitation towards developing it as a potential AD therapeutic. In this report, we use nanoscale AFM-IR spectroscopy to probe the structure of Aβ oligomers and fibrils at the single aggregate level and demonstrate that the main effect of β-carotene towards modulating Aβ aggregation is not to inhibit fibril formation but to alter the secondary structure of the fibrils and promote fibrils that lack the characteristic ordered beta structure.

Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; beta Carotene; Humans; Peptide Fragments; Protein Structure, Secondary

Topics: Acetylcholine; Acetylcholinesterase; Alzheimer Disease; Animals; beta Carotene; Cholinesterase Inhibitors; Molecular Docking Simulation; Pharmaceutical Preparations; Zebrafish

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer’s dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; beta Carotene; Dementia; Humans; Prospective Studies; Tocopherols; Vitamin A; Vitamin D; Vitamin D Deficiency; Vitamins

Advancing age represents the strongest risk factor for Alzheimer's disease (AD), and the identification of biomarkers able to define what characterizes physiological aging from AD may represent a potential starting point for novel preventive strategies. Among these biomarkers, telomeres seem to be a promising target. Interestingly, high intake of carotenoid-rich food may play a role in protecting telomeres by oxidative stress reduction. Accordingly, low plasma β-carotene concentrations have been found in AD subjects when compared with cognitively healthy subjects. In this study, we aim at investigating the hypothesis that low β-carotene might be associated with markers of accelerated cellular aging, including leucocyte telomere length (LTL) and peripheral mononuclear cell (PBMC) telomerase activity in a cohort of old age subjects.. The study was conducted in 68 old age subjects, 37 AD, and 31 age-matched healthy controls. In all subjects, β-carotene plasma level, LTL and peripheral telomerase activity were measured.. In all populations, β-carotene significantly and positively (r = 0.320, p = 0.008) correlated with telomerase activity, independent of gender. A model having telomerase activity levels as the dependent variable, and age, gender, smoking habit, and β-carotene as independent variables, confirmed that β-carotene was independently associated with telomerase activity (β = 0.319, p = 0.012). Subjects affected by AD had significantly lower plasmatic levels of β-carotene (448 ± 66 mg/ml vs 497 ± 59 mg/ml, p = 0.001) and LTL (0.53 ± 0.25 vs 0.69 ± 0.29; p = 0.009) as compared with healthy controls. Β-carotene plasma level was associated with AD diagnosis (OR 0.988; IC95% 0.978-0.997; p = 0.013) independently of age, gender, smoking habit, ApoE genotype, and LTL.. Our data show that β-carotene may modulate telomerase activity in old age. Moreover, lower plasma β-carotene levels, correlating with peripheral telomerase activity, are associated with AD diagnosis independent of multiple covariates.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; beta Carotene; Biomarkers; Cross-Sectional Studies; Female; Geriatric Assessment; Humans; Male; Telomerase

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a cascade of changes in cognitive, behavioral, and social activities. Several areas of the brain are involved in the regulation of memory. Of most importance are the amygdala and hippocampus. Antioxidant therapy is used for the palliative treatment of different degenerative diseases like diabetes, cirrhosis, and Parkinson's, etc. The objective of this study was to assess the effectiveness of exogenous antioxidants, in particular, β carotene (1.02 and 2.05 mg/kg) against intracerebroventricular injected streptozotocin-induced memory impairment in mice. Streptozotocin (3 mg/kg, i.c.v) was administered in two separate doses (on 1st and 3rd days of treatment) for neurodegeneration. Fifty Albino mice (male) were selected in the protocol, and they were classified into five groups (Group I-control, Group II-disease, Group III-standard, Group IV-V-β-carotene-treated) to investigate the cognitive enhancement effect of selected antioxidants. The cognitive performance was observed following the elevated plus-maze, passive avoidance, and open field paradigms. Acetylcholine esterase, β-amyloid protein, and biochemical markers of oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase were analyzed in brain homogenates. In silico activity against acetylcholinesterase (AChE) was determined by the molecular modeling of β-carotene. β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity. The in silico studies confirmed the binding capacity of β-carotene with the acetylcholinesterase enzyme. The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments. These results suggest that β-carotene could be useful for the treatment of neurodegenerative diseases such as Alzheimer's disease.

Topics: Acetylcholinesterase; Alzheimer Disease; Animals; Antioxidants; beta Carotene; Cholinesterase Inhibitors; Cognitive Dysfunction; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Mice; Models, Molecular; Neuroprotective Agents; Oxidative Stress; Streptozocin

Higher circulating antioxidant concentrations are associated with a lower risk of late-onset Alzheimer disease (AD) in observational studies, suggesting that diet-sourced antioxidants may be modifiable targets for reducing disease risk. However, observational evidence is prone to substantial biases that limit causal inference, including residual confounding and reverse causation.. In order to infer whether long-term circulating antioxidant exposure plays a role in AD etiology, we tested the hypothesis that AD risk would be lower in individuals with lifelong, genetically predicted increases in concentrations of 4 circulating antioxidants that are modifiable by diet.. Two-sample Mendelian randomization analyses were conducted. First, published genetic association studies were used to identify single-nucleotide polymorphisms (SNPs) that determine variation in circulating ascorbate (vitamin C), β-carotene, retinol (vitamin A), and urate. Second, for each set of SNP data, statistics for genotype associations with AD risk were extracted from data of a genome-wide association study of late-onset AD cases and controls (n = 17,008 and 37,154, respectively). Ratio-of-coefficients and inverse-variance-weighted meta-analyses were the primary methods used to assess the 4 sets of SNP-exposure and SNP-AD associations. Additional analyses assessed the potential impact of bias from pleiotropy on estimates.. The models suggested that genetically determined differences in circulating ascorbate, retinol, and urate are not associated with differences in AD risk. All estimates were close to the null, with all ORs for AD ≥1 per unit increase in antioxidant exposure (ranging from 1.00 for ascorbate to 1.05 for retinol). There was little evidence to imply that pleiotropy had biased results.. Our findings suggest that higher exposure to ascorbate, β-carotene, retinol, or urate does not lower the risk of AD. Replication Mendelian randomization studies could assess this further, providing larger AD case-control samples and, ideally, using additional variants to instrument each exposure.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Diet; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Uric Acid; Vitamin A

Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases that affect the neurons in the brain and the spinal cord. Neuroinflamation and apoptosis are key players in the progressive damage of the neurons in AD and ALS. Currently, there is no drug to offer complete cure for both these diseases. Riluzole is the only available drug that can prolong the life time of the ALS patients for nearly 3 months. Molecules that offer good HIT to the molecular targets of ALS will help to treat AD and ALS patients. P53 kinase receptor (4AT3), EphA4 (3CKH) and histone deacetylase (3SFF) are the promising disease targets of AD and ALS. This paper discusses on a new approach to combat neurodegenerative diseases using photosynthetic pigments. The docking studies were performed with the Autodock Vina algorithm to predict the binding of the natural pigments such as β carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin on these targets. The β carotene, phycoerythrin and phycocyanin had higher binding energies indicating the antagonistic activity to the disease targets. These pigments serve as a potential therapeutic molecule to treat neuroinflammation and apoptosis in the AD and ALS patients.

Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; beta Carotene; Chlorophyll; Chlorophyll A; Histone Deacetylases; Humans; Models, Molecular; Phycocyanin; Phycoerythrin; Protein Conformation; Receptor, EphA4

The in vitro effect of a vitamin complex in generating and reducing oxidative species in peripheral blood mononuclear cells (PBMNC) and plasma of patients with Alzheimer's disease (AD) and healthy subjects (HS) was evaluated.. Two concentrations of a vitamin complex ([A] and [20A]) with ascorbic acid, alpha-tocopherol, and beta-carotene were incubated with either mononuclear cells or plasma. The generation of oxidizing species was measured in a luminol-dependent chemiluminescence assay and the reducing response by the MTT dye reduction assay. The levels of cytokines (interleukin [IL]-1β, IL-6, and IL-4) were measured by sandwich enzyme-linked immunosorbent assay.. Our results demonstrated that the increase in the vitamin complex concentration reduced the reactive oxygen species (ROS) production and enhanced cellular reduction capacity in cells of AD patients in concentration [20A]. Plasma reduction capacity rose significantly for both groups (AD and HS). Concentration [A] did not alter the IL-1β production, increased IL-4 production in both groups and lowered IL-6 production in AD cells. Concentration [20A] increased pro-inflammatory cytokines (IL-1β and IL-6) and decreased IL-4 production by PBMNC of HS leading to a pro-inflammatory status.. The antioxidant vitamin complex was effective in reducing oxidative stress in PBMNC of AD patients by lowering ROS production, improving cellular antioxidant capacities and modifying cytokine induced inflammation.

Topics: Aged; Aged, 80 and over; alpha-Tocopherol; Alzheimer Disease; Antioxidants; Ascorbic Acid; beta Carotene; Female; Humans; Interleukin-1beta; Interleukin-4; Interleukin-6; Leukocytes, Mononuclear; Male; Middle Aged; Oxidative Stress; Reactive Oxygen Species

Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment. Fasting plasma carotenoids were measured in 36 AD subjects and 10 control subjects by HPLC. Correlations between plasma carotenoid levels, red blood cell (RBC) n-3 fatty acids, and dementia severity were examined in AD patients. Moderately severe AD patients (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and beta-carotene, compared to mild AD patients (MMSE=24-27) or controls. Among AD patients, variables (lutein, beta-carotene, RBC docosahexaenoic acid (DHA) and LDL-cholesterol) were significantly correlated with MMSE. A lower MMSE score was associated with lower lutein, beta-carotene and RBC DHA levels, and a higher LDL-cholesterol level. These variables explained the majority of variation in dementia severity (55% of variance in MMSE). Lutein, beta-carotene and beta-cryptoxanthin were positively correlated with RBC DHA in AD patients. The association between higher carotenoids levels and DHA and higher MMSE scores, supports a protective role of both types of nutrients in AD. These findings suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in strategies to slow the rate of cognitive decline.

Topics: Alzheimer Disease; beta Carotene; Biomarkers; Chromatography, High Pressure Liquid; Dementia; Docosahexaenoic Acids; Fasting; Humans; Lutein; Neuropsychological Tests; Nutritional Status; Severity of Illness Index

Topics: Alzheimer Disease; Antioxidants; beta Carotene; Clinical Trials as Topic; Cognition Disorders; Humans; Time Factors; Treatment Outcome; Vitamin E

Some research findings based on observational epidemiology are contradicted by randomized trials, but may nevertheless still be supported in some scientific circles.. To evaluate the change over time in the content of citations for 2 highly cited epidemiological studies that proposed major cardiovascular benefits associated with vitamin E in 1993; and to understand how these benefits continued being defended in the literature, despite strong contradicting evidence from large randomized clinical trials (RCTs). To examine the generalizability of these findings, we also examined the extent of persistence of supporting citations for the highly cited and contradicted protective effects of beta-carotene on cancer and of estrogen on Alzheimer disease.. For vitamin E, we sampled articles published in 1997, 2001, and 2005 (before, early, and late after publication of refuting evidence) that referenced the highly cited epidemiological studies and separately sampled articles published in 2005 and referencing the major contradicting RCT (HOPE trial). We also sampled articles published in 2006 that referenced highly cited articles proposing benefits associated with beta-carotene for cancer (published in 1981 and contradicted long ago by RCTs in 1994-1996) and estrogen for Alzheimer disease (published in 1996 and contradicted recently by RCTs in 2004).. The stance of the citing articles was rated as favorable, equivocal, and unfavorable to the intervention. We also recorded the range of counterarguments raised to defend effectiveness against contradicting evidence.. For the 2 vitamin E epidemiological studies, even in 2005, 50% of citing articles remained favorable. A favorable stance was independently less likely in more recent articles, specifically in articles that also cited the HOPE trial (odds ratio for 2001, 0.05 [95% confidence interval, 0.01-0.19; P < .001] and the odds ratio for 2005, 0.06 [95% confidence interval, 0.02-0.24; P < .001], as compared with 1997), and in general/internal medicine vs specialty journals. Among articles citing the HOPE trial in 2005, 41.4% were unfavorable. In 2006, 62.5% of articles referencing the highly cited article that had proposed beta-carotene and 61.7% of those referencing the highly cited article on estrogen effectiveness were still favorable; 100% and 96%, respectively, of the citations appeared in specialty journals; and citations were significantly less favorable (P = .001 and P = .009, respectively) when the major contradicting trials were also mentioned. Counterarguments defending vitamin E or estrogen included diverse selection and information biases and genuine differences across studies in participants, interventions, cointerventions, and outcomes. Favorable citations to beta-carotene, long after evidence contradicted its effectiveness, did not consider the contradicting evidence.. Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials.

Topics: Alzheimer Disease; beta Carotene; Epidemiologic Studies; Estrogens; Evidence-Based Medicine; Humans; Neoplasms; Observation; Publication Bias; Randomized Controlled Trials as Topic; Vitamin E; Vitamins

Antioxidants have been hypothesized to protect against Alzheimer's disease, but studies conducted in late life have been inconsistent. Risk factors measured in midlife may better predict dementia in late life because they are less affected by the disease process. The authors examined the association of midlife dietary intake of antioxidants to late-life dementia and its subtypes. Data were obtained from the Honolulu-Asia Aging Study, a prospective community-based study of Japanese-American men who were aged 45-68 years in 1965-1968, when a 24-hour dietary recall was administered. The analysis included 2,459 men with complete dietary data who were dementia-free at the first assessment in 1991-1993 and were examined up to two times for dementia between 1991 and 1999. The sample included 235 incident cases of dementia (102 cases of Alzheimer's disease, 38 cases of Alzheimer's disease with contributing cerebrovascular disease, and 44 cases of vascular dementia). Relative risks by quartile of intake were calculated using Cox proportional hazards models with age as the time scale, after adjustment for sociodemographic and lifestyle factors, cardiovascular risk factors, other dietary constituents, and apolipoprotein E e4. Intakes of beta-carotene, flavonoids, and vitamins E and C were not associated with the risk of dementia or its subtypes. This analysis suggests that midlife dietary intake of antioxidants does not modify the risk of late-life dementia or its most prevalent subtypes.

Topics: Age Distribution; Aged; Aging; Alzheimer Disease; Antioxidants; Ascorbic Acid; Asian; beta Carotene; Dementia; Dementia, Vascular; Diet Surveys; Feeding Behavior; Flavonoids; Hawaii; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Risk Assessment; Smoking; Vitamin E

Cerebral deposition of amyloid beta-peptide (Abeta) in the brain is an invariant feature of Alzheimer disease (AD). Plasma or cerebrospinal fluid concentrations of antioxidant vitamins and carotenoids, such as vitamins A, C, E, and beta-carotene, have been reported to be lower in AD patients, and these vitamins clinically have been demonstrated to slow the progression of dementia. In this study, we used fluorescence spectroscopy with thioflavin T (ThT) and electron microscopy to examine the effects of vitamin A (retinol, retinal, and retinoic acid), beta-carotene, and vitamins B2, B6, C, and E on the formation, extension, and destabilization of beta-amyloid fibrils (fAbeta) in vitro. Among them, vitamin A and beta-carotene dose-dependently inhibited formation of fAbeta from fresh Abeta, as well as their extension. Moreover, they dose-dependently destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of retinol = retinal > beta-carotene > retinoic acid. Although the exact mechanisms are still unclear, vitamins A and beta-carotene could be key molecules for the prevention and therapy of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Benzothiazoles; beta Carotene; Cell Line; Dose-Response Relationship, Drug; Humans; Kinetics; Microscopy, Electron; Molecular Structure; Neurofibrils; Retinaldehyde; Thiazoles; Tretinoin; Vitamin A; Vitamins

Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress.. To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease.. The Rotterdam Study, a population-based, prospective cohort study conducted in the Netherlands.. A total of 5395 participants who, at baseline (1990-1993), were aged at least 55 years, free of dementia, and noninstitutionalized and had reliable dietary assessment. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia.. Incidence of Alzheimer disease, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria, associated with dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E.. After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had Alzheimer disease. When adjustments were made for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease (rate ratios [RRs] per 1-SD increase in intake were 0.82 [95% confidence interval [CI], 0.68-0.99] and 0.82 [95% CI, 0.66-1.00], respectively). Among current smokers, this relationship was most pronounced (RRs, 0.65 [95% CI, 0.37-1.14] and 0.58 [95% CI, 0.30-1.12], respectively) and also was present for intake of beta carotene (RR, 0.49 [95% CI, 0.27-0.92]) and flavonoids (RR, 0.54 [95% CI, 0.31-0.96]). The associations did not vary by education or apolipoprotein E genotype.. High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease.

Topics: Aged; Alzheimer Disease; Antioxidants; Ascorbic Acid; beta Carotene; Dementia; Dietary Supplements; Female; Flavonoids; Humans; Male; Middle Aged; Nutrition Assessment; Oxidative Stress; Proportional Hazards Models; Prospective Studies; Risk; Vitamin E

Oxidative processes have been suggested as elements in the development of Alzheimer disease (AD), but whether dietary intake of vitamin E and other antioxidant nutrients prevents its development is unknown.. To examine whether intake of antioxidant nutrients, vitamin E, vitamin C, and beta carotene is associated with incident AD.. Prospective study, conducted from 1993 to 2000, of individuals selected in a stratified random sample of community-dwelling residents. The 815 residents 65 years and older were free of AD at baseline and were followed up for a mean of 3.9 years. They completed food frequency questionnaires an average of 1.7 years after baseline.. Incident AD diagnosed in clinical evaluations with standardized criteria.. Increasing vitamin E intake from foods was associated with decreased risk of developing AD after adjustment for age, education, sex, race, APOE epsilon 4, and length of follow-up. Relative risks (95% confidence intervals [CIs]) from lowest to highest quintiles of intake were 1.00, 0.71 (0.24-2.07), 0.62 (0.26-1.45), 0.71 (0.27-1.88), and 0.30 (0.10-0.92) (P for trend =.05). The protective association of vitamin E was observed only among persons who were APOE epsilon 4 negative. Adjustment for other dietary factors reduced the protective association. After adjustment for baseline memory score, the risk was 0.36 (95% CI, 0.11-1.17). Intake of vitamin C, beta carotene, and vitamin E from supplements was not significantly associated with risk of AD.. This study suggests that vitamin E from food, but not other antioxidants, may be associated with a reduced risk of AD. Unexpectedly, this association was observed only among individuals without the APOE epsilon 4 allele.

Topics: Aged; Alzheimer Disease; Antioxidants; Apolipoprotein E4; Apolipoproteins E; Ascorbic Acid; beta Carotene; Black People; Cluster Analysis; Dietary Supplements; Female; Humans; Male; Models, Statistical; Nutrition Assessment; Oxidative Stress; Prospective Studies; Risk; Vitamin E; White People

Oxidation has been proposed to be an important factor in the pathogenesis of Alzheimer's disease (AD) and amyloid beta is considered to induce oxidation. In biological fluids, including cerebrospinal fluid (CSF), amyloid beta is found complexed to lipoproteins. On the basis of these observations, we investigated the potential role of lipoprotein oxidation in the pathology of AD. Lipoprotein oxidizability was measured in vitro in CSF and plasma from 29 AD patients and found to be significantly increased in comparison to 29 nondemented controls. The levels of the hydrophilic antioxidant ascorbate were significantly lower in CSF and plasma from AD patients. In plasma, alpha-carotene was significantly lower in AD patients compared to controls while alpha-tocopherol levels were indistinguishable between patients and controls. In CSF, a nonsignificant trend to lower alpha-tocopherol levels among AD patients was found. Polyunsaturated fatty acids, the lipid substrate for oxidation, were significantly lower in the CSF of AD patients. Our findings suggest that (i) lipoprotein oxidation may be important in the development of AD and (ii) the in vitro measurement of lipid peroxidation in CSF might become a useful additional marker for diagnosis of AD.

Topics: Age Factors; Aged; Alzheimer Disease; Apolipoproteins E; beta Carotene; Cholesterol; Fatty Acids, Nonesterified; Female; Genotype; Humans; Lipoproteins; Male; Middle Aged; Oxidation-Reduction; Reference Values; Smoking; Triglycerides; Vitamin E

In a case/control study, serum concentrations of vitamins A and E and major carotenoids were determined in patients with Alzheimer's disease, multi-infarct dementia and control subjects. The results showed that both Alzheimer's and multi-infarct dementia patients had significantly lower levels of vitamin E and beta-carotene than controls (vitamin E: 18.65 +/- 3.62 mumol/l in Alzheimer's disease and 15.80 +/- 6.93 mumol/l in multi-infarct dementia versus 30.03 +/- 12.03 mumol/l in controls; beta-carotene less than 0.13 to 0.42 mumol/l in Alzheimer's disease and less than 0.13 to 0.30 mumol/l in multi-infarct dementia versus 0.13 to 1.53 mumol/l in controls). Vitamin A was significantly reduced only in the Alzheimer's patients (1.56 +/- 0.78 mumol/l in Alzheimer's disease versus 2.13 +/- 0.86 mumol/l in controls).

Topics: Aged; Aged, 80 and over; Alzheimer Disease; beta Carotene; Carotenoids; Dementia, Multi-Infarct; Female; Free Radicals; Humans; Male; Reference Values; Vitamin A; Vitamin E