Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a north Indian population

PURPOSE. To examine the association of blood antioxidants with cataract.

Carotenoids and co-antioxidants in age-related maculopathy:design and methods

Age-related macular degeneration (AMD), is the leading cause of blind registration in the Western World among individuals 65 years or older. Early AMD, a clinical state without overt functional loss, is said to be present clinically when yellowish deposits known as drusen and/or alterations of fundus pigmentation are seen in the macular retina. Although the etiopathogenesis of AMD remains uncertain, there is a growing body of evidence in support of the view that cumulative oxidative damage plays a causal role. Appropriate dietary antioxidant supplementation is likely to be beneficial in maintaining visual function in patients with AMD, and preventing or delaying the progression of early AMD to late AMD. The Carotenoids in Age-Related Maculopathy (CARMA) Study is a randomized and double-masked clinical trial of antioxidant supplementation versus placebo in 433 participants with either early AMD features of sufficient severity in at least one eye or any level of AMD in one eye with late AMD (neovascular AMD or central geographic atrophy) in the fellow eye. The aim of the CARMA Study is to investigate whether lutein and zeaxanthin, in combination with co-antioxidants (vitamin C, E, and zinc), has a beneficial effect on visual function and/or prevention of progression from early to late stages of disease. The primary outcome is improved or preserved distance visual acuity at 12 months. Secondary outcomes include improved or preserved interferometric acuity, contrast sensitivity, shape discrimination ability, and change in AMD severity as monitored by fundus photography. This article outlines the CARMA Study design and methodology, including its rationale.

Secondary Outcomes in a Clinical Trial of Carotenoids with Coantioxidants versus Placebo in Early Age-Related Macular Degeneration

Purpose: To report the secondary outcomes in the Carotenoids with Coantioxidants in Age-Related Maculopathy trial.

Design: Randomized double-masked placebo-controlled clinical trial (registered as ISRCTN 94557601).

Participants: Participants included 433 adults 55 years of age or older with early age-related macular degeneration (AMD) in 1 eye and late-stage disease in the fellow eye (group 1) or early AMD in both eyes (group 2).

Intervention: An oral preparation containing lutein (L), zeaxanthin (Z), vitamin C, vitamin E, copper, and zinc or placebo. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), Raman spectroscopy, stereoscopic colour fundus photography, and serum sampling were performed every 6 months with a minimum follow-up time of 12 months.

Main Outcome Measures: Secondary outcomes included differences in BCVA (at 24 and 36 months), CS, Raman counts, serum antioxidant levels, and progression along the AMD severity scale (at 12, 24, and 36 months).

Results: The differential between active and placebo groups increased steadily, with average BCVA in the former being approximately 4.8 letters better than the latter for those who had 36 months of follow-up, and this difference was statistically significant (P = 0.04). In the longitudinal analysis, for a 1-log-unit increase in serum L, visual acuity was better by 1.4 letters (95% confidence interval, 0.3-2.5; P = 0.01), and a slower progression along a morphologic severity scale (P = 0.014) was observed.

Conclusions: Functional and morphologic benefits were observed in key secondary outcomes after supplementation with L, Z, and coantioxidants in persons with early AMD.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.

Investigation of Genetic Variation in Scavenger Receptor Class B, Member 1 (SCARB1) and Association with Serum Carotenoids

Objective: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD).
Design: A cross-sectional study of healthy adults aged 20 to 70.
Participants: We recruited 302 participants after local advertisement.
Methods: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts.
Main Outcome Measures: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender.
Results: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10-4), an SNP in high linkage disequilibrium with rs11057841 (r2 = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses.
Conclusions: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina.
Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references. Ophthalmology 2013;120:1632–1640 © 2013 by the American Academy of Ophthalmology.

Serum carotenoids and fat-soluble vitamins in women with type 1 diabetes and preeclampsia:a longitudinal study

Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 diabetes. Prospective measures of fat-soluble vitamins in diabetic pregnancy are therefore of interest.

Carotenoids and health in older people

As the proportion of older people increases, so will chronic disease incidence and the proportion of the population living with disability. Therefore, new approaches to maintain health for as long as possible in this age group are required. Carotenoids are a group of polyphenolic compounds found predominantly in fruit and vegetables that have been proposed to have anti-inflammatory and antioxidant effects. Such properties may impact on the risk diseases which predominate in older people, and also ageing-related physiological changes. Working out the effect of carotenoid intake versus fruit and vegetable intake is difficult, and the strong correlation between individual carotenoid intakes also complicates any attempt to examine individual carotenoid health effects. Similarly, research to determine whether carotenoids consumed as supplements have similar benefits to increased dietary intake through whole foods, is still required. However, reviewing the recent evidence suggests that carotenoid intake and status are relatively consistently associated with reduced CVD risk, although β-carotene supplementation does not reduce CVD risk and increases lung cancer risk. Increased lycopene intake may reduce prostate cancer progression, with a potential role for carotenoids at other cancer sites. Lutein and zeaxanthin have a plausible role in the maintenance of eye health, whilst an association between carotenoid intake and cognitive and physical health appears possible, although research is limited to date. Given this accruing evidence base to support a specific role for certain carotenoids and ageing, current dietary advice to consume a diet rich in fruit and vegetables would appear prudent, and efforts maintained to encourage increased intake.

Antioxidants and periodontitis in 60-70 year- old men

Objective: The aim was to investigate the association between periodontal health and the serum levels of various antioxidants including carotenoids, retinol and vitamin E in a homogenous group of Western European men.
Materials and Methods: A representative sample of 1258 men aged 60-70 years, drawn from the population of Northern Ireland, was examined between 2001 and 2003. Each participant had six or more teeth, completed a questionnaire and underwent a clinical periodontal examination. Serum lipid-soluble antioxidant levels were measured by high-performance liquid chromatography with diode array detection. Multivariable analysis was carried out using logistic regression with adjustment for possible confounders. Models were constructed using two measures of periodontal status (low- and high-threshold periodontitis) as dependent variables and the fifths of each antioxidant as a predictor variable.
Results: The levels of a- and ß-carotene, ß-cryptoxanthin and zeaxanthin were highly significantly lower in the men with low-threshold periodontitis (p<0.001). These carotenoids were also significantly lower in high-threshold periodontitis. There were no significant differences in the levels of lutein, lycopene, a- and ?-tocopherol or retinol in relation to periodontitis. In fully adjusted models, there was an inverse relationship between a number of carotenoids (a- and ß-carotene and ß-cryptoxanthin) and low-threshold periodontitis. ß-Carotene and ß-cryptoxanthin were the only antioxidants that were associated with an increased risk of high-threshold severe periodontitis. The adjusted odds ratio for high-threshold periodontitis in the lowest fifth relative to the highest fifth of ß-cryptoxanthin was 4.02 (p=0.003).
Conclusion: It is concluded that low serum levels of a number of carotenoids, in particular beta-cryptoxanthin and beta-carotene, were associated with an increased prevalence of periodontitis in this homogenous group of 60-70-year-old Western European men.

Apolipoprotein E genotype is associated with macular pigment optical density.

PURPOSE: Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk factors for this condition may be classified as genetic and environmental. Apolipoprotein E is putatively involved in the transport of the macular pigment (MP) carotenoids lutein (L) and zeaxanthin (Z) in serum and may also influence retinal capture of these compounds. This study was designed to investigate the relationship between macular pigment optical density (MPOD) and ApoE genotype. METHODS: This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. Serum L and Z were measured by HPLC. ApoE genotyping was performed by direct polymerase chain reaction amplification and DNA nucleotide sequencing from peripheral blood. RESULTS: Genotype data were available on 300 of the 302 (99.3%) subjects. The mean (+/- SD) age of the subjects in this study was 47.89 +/- 11.05 (range, 21-66) years. Subjects were classed into one of three ApoE genotype groups, as follows: group 1, epsilon2epsilon2 or epsilon2epsilon3; group 2, epsilon3epsilon3; group 3, epsilon2epsilon4 or epsilon3epsilon4 or epsilon4epsilon4. All three groups were statistically comparable in terms of age, sex, body mass index, cigarette smoking, and dietary and serum levels of L and Z. There was a statistically significant association between ApoE genotype and MPOD. Subjects who had at least one epsilon4 allele had a higher MPOD across the macula than subjects without this allele (group 1 MPOD area, 0.70 +/- 0.40; group 2 MPOD area, 0.67 +/- 0.42; group 3 MPOD area, 0.85 +/- 0.46; one-way ANOVA, P = 0.014. CONCLUSIONS: These results suggest that ApoE genotype status is associated with MPOD. This association may explain, at least in part, the putative protective effect of the epsilon4 allele for AMD and is consistent with the view that apolipoprotein profile influences the transport and/or retinal capture of circulating L and/or Z.

Dietary antioxidant and mineral intake in humans is associated with reduced risk of esophageal adenocarcinoma but not reflux esophagitis or Barrett's esophagus

The role of antioxidants in the pathogenesis of reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) remains unknown. We evaluated the associations among dietary antioxidant intake and these diseases. We performed an assessment of dietary antioxidant intake in a case control study of RE (n = 219), BE (n = 220), EAC (n = 224), and matched population controls (n = 256) (the Factors Influencing the Barrett's Adenocarcinoma Relationship study) using a modification of a validated FFQ. We found that overall antioxidant index, a measure of the combined intake of vitamin C, vitamin E, total carotenoids, and selenium, was associated with a reduced risk of EAC [odds ratio (OR) = 0.57; 95% CI = 0.33-0.98], but not BE (OR = 0.95; 95% CI = 0.53-1.71) or RE (OR = 1.60; 95% CI = 0.86-2.98), for those in the highest compared with lowest category of intake. Those in the highest category of vitamin C intake had a lower risk of EAC (OR = 0.37; 95% CI = 0.21-0.66; P-trend = 0.001) and RE (OR = 0.46; 95% CI = 0.24-0.90; P-trend = 0.03) compared with those in the lowest category. Vitamin C intake was not associated with BE, and intake of vitamin E, total carotenoids, zinc, copper, or selenium was not associated with EAC, BE, or RE. In conclusion, the overall antioxidant index was associated with a reduced risk of EAC. Higher dietary intake of vitamin C was associated with a reduced risk of EAC and RE. These results suggest that antioxidants may play a role in the pathogenesis of RE and EAC and may be more important in terms of progression rather than initiation of the disease process.

The association between macular pigment optical density and CFH, ARMS2, C2/BF, and C3 genotype.

Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk for this condition may be classified as genetic or environmental, with an interaction between such factors predisposing to this disease. This study investigated the relationship between AMD risk genes, macular pigment optical density (MPOD), which may protect against AMD, and serum concentrations of the macular carotenoids, lutein (L) and zeaxanthin (Z). This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. We also calculated MPOD Area as the area of MP under the spatial profile curve, to reflect MP across the macula. Serum L and Z were measured by HPLC. Genotyping of tag SNPs in the genes CFH, ARMS2, C3, C2 and BF was undertaken with multiplex polymerase chain reaction (PCR) and primer extension methodology (ABI Snapshot, ABI Warrington UK) on DNA extracted from peripheral blood. The mean ± SD (range) age of the subjects in this study was 48 ± 11 (21-66) years. There was a statistically significant association between CFH genotype and family history of AMD, with subjects having two non-risk CFH haplotypes (n =35), or one non-risk and one protective CFH haplotype (n = 33), being significantly more likely to have a negative family history of AMD (Pearson Chi square: p = 0.001). There was no significant association between the AMD risk genes investigated and either MPOD (One way ANOVA: p > 0.05) or serum concentrations of L or Z (One way ANOVA: p > 0.05, for both). Subjects who were homozygous for risk alleles of both CFH and ARMS2 (n = 4) had significantly lower MPOD at 0.5_ and 1_ retinal eccentricity (Independent samples t test: p

Biomarkers of fruit and vegetable intake in Human intervention studies a systematic review

Observational evidence consistently shows that consumption of a diet rich in fruit and vegetables may offer protection against diseases such as cardiovascular disease and cancer. Assessment of dietary intake is complex and prone to many sources of error. More objective biomarkers of fruit and vegetable intake are therefore of interest. The aim of this review is to examine the usefulness of the main biomarkers of fruit and vegetable intake to act as objective indicators of compliance in dietary intervention studies. A comprehensive search of the literature was conducted using six databases. Suitable papers were selected and relevant data extracted. The papers were categorized into 3 sub-groups: whole diet interventions; mixed fruit and vegetable interventions; and studies involving individual varieties of fruits or vegetables. Ninety-six studies were included in the review. Overall, the most commonly measured, and most consistently responsive, biomarkers were the carotenoids and vitamin C. Based on the results of this systematic review, it remains prudent to measure a panel of biomarkers in fruit and vegetable intervention studies. The only possible exception to this is “fruit only” intervention studies where assessment of vitamin C alone may suffice.

Green tea supplementation increases glutathione and plasma antioxidant capacity in adults with the metabolic syndrome

Green tea, a popular polyphenol-containing beverage, has been shown to alleviate clinical features of the metabolic syndrome. However, its effects in endogenous antioxidant biomarkers are not clearly understood. Thus, we tested the hypothesis that green tea supplementation will upregulate antioxidant parameters (enzymatic and nonenzymatic) in adults with the metabolic syndrome. Thirty-five obese participants with the metabolic syndrome were randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day). Blood samples and dietary information were collected at baseline (0 week) and 8 weeks of the study. Circulating carotenoids (a-carotene, ß-carotene, lycopene) and tocopherols (a-tocopherol, ?-tocopherol) and trace elements were measured using high-performance liquid chromatography and inductively coupled plasma mass spectroscopy, respectively. Serum antioxidant enzymes (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity were measured spectrophotometrically. Green tea beverage and green tea extract significantly increased plasma antioxidant capacity (1.5 to 2.3 µmol/L and 1.2 to 2.5 µmol/L, respectively; P <.05) and whole blood glutathione (1783 to 2395 µg/g hemoglobin and 1905 to 2751 µg/g hemoglobin, respectively; P <.05) vs controls at 8 weeks. No effects were noted in serum levels of carotenoids and tocopherols and glutathione peroxidase and catalase activities. Green tea extract significantly reduced plasma iron vs baseline (128 to 92 µg/dL, P <.02), whereas copper, zinc, and selenium were not affected. These results support the hypothesis that green tea may provide antioxidant protection in the metabolic syndrome.

A randomised controlled trial of increasing fruit and vegetable intake and how this influences the carotenoid concentration and activities of PON-1 and LCAT in HDL from subjects with type 2 diabetes

Background

High density lipoproteins (HDL) have many cardioprotective roles; however, in subjects with type 2 diabetes (T2D) these cardioprotective properties are diminished. Conversely, increased fruit and vegetable (F&V) intake may reduce cardiovascular disease risk, although direct trial evidence of a mechanism by which this occurs in subjects with T2D is lacking. Therefore, the aim of this study was to examine if increased F&V consumption influenced the carotenoid content and enzymes associated with the antioxidant properties of HDL in subjects with T2D.

Eighty obese subjects with T2D were randomised to a 1- or ≥6-portion/day F&V diet for 8-weeks. Fasting serum was collected pre- and post-intervention. HDL was subfractionated into HDL₂ and HDL₃ by rapid ultracentrifugation. Carotenoids were measured in serum, HDL₂ and HDL₃ by high performance liquid chromatography. The activity of paraoxonase-1 (PON-1) was measured in serum, HDL₂ and HDL₃ by a spectrophotometric assay, while the activity of lecithin cholesterol acyltransferase (LCAT) was measured in serum, HDL₂ and HDL₃ by a fluorometric assay.

In the ≥6- vs. 1-portion post-intervention comparisons, carotenoids increased in serum, HDL₂ and particularly HDL₃, (α-carotene, p = 0.008; β-cryptoxanthin, p = 0.042; lutein, p = 0.012; lycopene, p = 0.016), as did the activities of PON-1 and LCAT in HDL₃ (p = 0.006 and 0.044, respectively).

To our knowledge, this is the first study in subjects with T2D to demonstrate that increased F&V intake augmented the carotenoid content and influenced enzymes associated with the antioxidant properties of HDL. We suggest that these changes would enhance the cardioprotective properties of this lipoprotein.

Fruits and vegetables:measuring intake and encouraging increased consumption

A high intake of fruit and vegetables (FV) is associated with reduced risk of chronic disease, although the evidence base is mostly observational. Blood biomarkers offer an objective indicator of FV intake, potentially improving estimates of intakes based on traditional methods. A valid biomarker of overall FV intake would be able to confirm population intakes, more precisely evaluate the association between intakes and health outcomes and confirm compliance in FV interventions. Several substances have been proposed as biomarkers of FV intake: vitamin C, the carotenoids and polyphenols. Certain biomarkers are strong predictors of single FV; however, the proposed single biomarkers of FV consumption are only modestly predictive of overall FV consumption. This is likely to be due to the complexity of the FV food group. While accurately measuring FV intake is important in nutrition research, another critical question is: how best can an increase in FV intake be achieved? Increased FV intake has been achieved in efficacy studies using intensive dietary advice. Alternative, less intensive methods for encouraging FV consumption need to be developed and tested for population level intervention. Systematic reviews suggest peer support to be an effective strategy to promote dietary change. This review will describe the evidence for a link between increased FV intake and good health, outline possible novel biomarkers of FV consumption, present the most recently available data on population intake of FV and examine the usefulness of different approaches to encourage increased consumption of FV.