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JAMA Ophthalmology Jul 2022After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up.
OBJECTIVE
To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD).
DESIGN, SETTING, AND PARTICIPANTS
This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022.
INTERVENTIONS
During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively.
MAIN OUTCOMES AND MEASURES
Self-reported lung cancer and late AMD validated with medical records.
RESULTS
This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48).
CONCLUSIONS AND RELEVANCE
Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.
Topics: Aged; Dietary Supplements; Fatty Acids, Omega-3; Female; Follow-Up Studies; Humans; Lung Neoplasms; Macular Degeneration; Zeaxanthins; Zinc; beta Carotene
PubMed: 35653117
DOI: 10.1001/jamaophthalmol.2022.1640 -
BioMed Research International 2022Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of... (Review)
Review
Oxidative stress is one of the common factors leading to age-related eye diseases in older adults. Factors such as high oxygen consumption, high concentration of polyunsaturated fatty acids, and cumulative exposure to high-energy visible light in the eyes, lead to excessive generation of reactive oxygen species, hence triggering apoptosis of ocular cells and giving rise to ophthalmic diseases. Dietary supplements such as carotenoids, anthocyanins, and vitamins have antioxidant properties which may be of benefit in retaining better vision or reversing vision impairment; thus, studies have been conducted to understand the role of dietary supplements in the treatment or prevention of ophthalmic diseases. While high concentration of carotenoids such as lutein and zeaxanthin decrease the risk of developing age-related macular disease, anthocyanins and vitamins play a role in the treatment and prevention of other ophthalmic diseases: saffron extract reduced intraocular pressure in glaucoma patients; bilberry extract prevented impairments in lenses and retina, as well as alleviate symptoms of dry eye disease; high concentration of beta-carotene may reduce the risk of developing cataract. Further studies with clinical measurements are required to investigate the effectiveness of antioxidants on visual function and ophthalmic diseases.
Topics: Aged; Aging; Anthocyanins; Antioxidants; Carotenoids; Dietary Supplements; Humans; Lutein; Reactive Oxygen Species; Retina; Vitamin A; Vitamins; Zeaxanthins; beta Carotene
PubMed: 36225983
DOI: 10.1155/2022/5810373 -
Nutrients Mar 2022Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in... (Meta-Analysis)
Meta-Analysis Review
Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06-1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08-1.35) and non-medics (RR = 1.18, 95% CI = 1.07-1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer.
Topics: Antioxidants; Dietary Supplements; Humans; Lung Neoplasms; Smoking; beta Carotene
PubMed: 35405977
DOI: 10.3390/nu14071361 -
Molecules (Basel, Switzerland) Oct 2022The current review provides an up-to-date analysis of scientific data on astaxanthin (ASX) sources and experimental studies on its health benefits as a potent... (Review)
Review
The current review provides an up-to-date analysis of scientific data on astaxanthin (ASX) sources and experimental studies on its health benefits as a potent antioxidant in the aging process. ASX is a liposoluble carotenoid nutrient and reddish-orange pigment, naturally synthesized by numerous microalgae, yeasts, and bacteria as secondary metabolites. Provides a reddish hue to redfish and shellfish flesh that feed on ASX-producing microorganisms. The microalga is the most important source for its industrial bioproduction. Due to its strong antioxidant properties, numerous investigations reported that natural ASX is a more significant antioxidant agent than other antioxidants, such as vitamin C, vitamin E, and β-carotene. Furthermore, several data show that ASX possesses important nutraceutical applications and health benefits, especially in healthy aging processes. However, further studies are needed for a deeper understanding of the potential mechanisms through which ASX could lead to its effective role in the healthy aging process, such as supporting brain health and skin homeostasis. This review highlights the current investigations on the effective role of ASX in oxidative stress, aging mechanisms, skin physiology, and central nervous system functioning, and shows the potential clinical implications related to its consumption.
Topics: Antioxidants; Xanthophylls; Dietary Supplements; beta Carotene
PubMed: 36363994
DOI: 10.3390/molecules27217167 -
Acta Ophthalmologica Dec 2022The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on... (Review)
Review
The aim of this paper is to summarize all available evidence from systematic reviews, randomized controlled trials (RCTs) and comparative nonrandomized studies (NRS) on the association between nutrition and antioxidant, vitamin, and mineral supplements and the development or progression of age-related macular degeneration (AMD). The Cochrane Database of Systematic Reviews, Cochrane register CENTRAL, MEDLINE and Embase were searched and studies published between January 2015 and May 2021 were included. The certainty of evidence was assessed according to the GRADE methodology. The main outcome measures were development of AMD, progression of AMD, and side effects. We included 7 systematic reviews, 7 RCTs, and 13 NRS. A high consumption of specific nutrients, i.e. β-carotene, lutein and zeaxanthin, copper, folate, magnesium, vitamin A, niacin, vitamin B6, vitamin C, docosahexaenoic acid, and eicosapentaenoic acid, was associated with a lower risk of progression of early to late AMD (high certainty of evidence). Use of antioxidant supplements and adherence to a Mediterranean diet, characterized by a high consumption of vegetables, whole grains, and nuts and a low consumption of red meat, were associated with a decreased risk of progression of early to late AMD (moderate certainty of evidence). A high consumption of alcohol was associated with a higher risk of developing AMD (moderate certainty of evidence). Supplementary vitamin C, vitamin E, or β-carotene were not associated with the development of AMD, and supplementary omega-3 fatty acids were not associated with progression to late AMD (high certainty of evidence). Research in the last 35 years included in our overview supports that a high intake of specific nutrients, the use of antioxidant supplements and adherence to a Mediterranean diet decrease the risk of progression of early to late AMD.
Topics: Humans; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Macular Degeneration; Vitamins
PubMed: 35695158
DOI: 10.1111/aos.15191 -
ELife Sep 2020Carotenoids are essential in oxygenic photosynthesis: they stabilize the pigment-protein complexes, are active in harvesting sunlight and in photoprotection. In plants,...
Carotenoids are essential in oxygenic photosynthesis: they stabilize the pigment-protein complexes, are active in harvesting sunlight and in photoprotection. In plants, they are present as carotenes and their oxygenated derivatives, xanthophylls. While mutant plants lacking xanthophylls are capable of photoautotrophic growth, no plants without carotenes in their photosystems have been reported so far, which has led to the common opinion that carotenes are essential for photosynthesis. Here, we report the first plant that grows photoautotrophically in the absence of carotenes: a tobacco plant containing only the xanthophyll astaxanthin. Surprisingly, both photosystems are fully functional despite their carotenoid-binding sites being occupied by astaxanthin instead of β-carotene or remaining empty (i.e. are not occupied by carotenoids). These plants display non-photochemical quenching, despite the absence of both zeaxanthin and lutein and show that tobacco can regulate the ratio between the two photosystems in a very large dynamic range to optimize electron transport.
Topics: Photosynthesis; Plants, Genetically Modified; Nicotiana; Xanthophylls; beta Carotene
PubMed: 32975516
DOI: 10.7554/eLife.58984 -
Nutrients Oct 2022Previous observational studies have suggested that the effect of diet-derived circulating micronutrient concentrations on lung cancer (LC) risk is controversial. We... (Meta-Analysis)
Meta-Analysis
Previous observational studies have suggested that the effect of diet-derived circulating micronutrient concentrations on lung cancer (LC) risk is controversial. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between circulating micronutrient concentrations and the overall risk of LC and three LC subtypes (namely lung adenocarcinoma (LA), squamous cell lung cancer (SqCLC), and small cell lung cancer (SCLC)). The instrumental variables (IVs) of 11 micronutrients (beta-carotene, calcium, copper, folate, lycopene, magnesium, phosphorus, retinol, selenium, zinc, and vitamin B6) were screened from the published genome-wide association studies (GWAS). Summary statistics related to LC and its subtypes came from the largest meta-analysis, including 29,266 cases and 56,450 controls. Inverse-variance weighted (IVW) method is used as the main MR analysis, and the sensitivity analysis is carried out to ensure the MR assumptions. This MR study found suggestive evidence that genetically predicted 6 circulating micronutrient concentrations was correlated with the risk of overall LC (odds ratio (OR): 1.394, 95% confidence interval (CI): 1.041-1.868, = 0.026, phosphorus), LA (OR: 0.794, 95% CI: 0.634-0.995, = 0.045, beta-carotene; OR: 0.687, 95%CI: 0.494-0.957, = 0.026, calcium), SqCLC (OR: 0.354, 95% CI: 0.145-0.865, = 0.023, retinol), and SCLC (OR: 1.267, 95% CI: 1.040-1.543, = 0.019, copper; OR: 0.801, 95% CI: 0.679-0.944, = 0.008, zinc). We found no evidence that other micronutrients are associated with the risk of overall LC or its subtypes. Our study suggested that the increase in circulating beta-carotene, calcium, retinol, and zinc concentration may reduce the risk of LC; the increase in circulating copper and phosphorus concentration may be related to the increased risk of LC. In the future, larger replication samples of LC genetic data and larger micronutrient-related GWAS will be needed to verify our findings.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; beta Carotene; Micronutrients; Vitamin A; Calcium; Copper; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Zinc; Phosphorus; Polymorphism, Single Nucleotide
PubMed: 36364831
DOI: 10.3390/nu14214569 -
Ophthalmology Mar 2020
Topics: Eye Diseases; Fatty Acids, Omega-3; Humans; Lutein; Macular Degeneration; Zeaxanthins; Zinc; beta Carotene
PubMed: 32087877
DOI: 10.1016/j.ophtha.2019.10.033 -
Food and Chemical Toxicology : An... Jun 2021β-Carotene oxidation products have newly discovered bioactivity in plants and animals. Synthetic fully oxidized β-carotene (OxBC) has application in supporting...
β-Carotene oxidation products have newly discovered bioactivity in plants and animals. Synthetic fully oxidized β-carotene (OxBC) has application in supporting livestock health, with potential human applications. The safety of synthetic OxBC has been evaluated. An Ames test showed weak-to-moderate mutagenicity in only one cell line at high concentrations. A mouse micronucleus assay established a non-toxic dose of 1800 mg/kg body weight, and no bone marrow micronuclei were induced. Plant sources of β-carotene inevitably contain varying levels of natural OxBC. Vegetable powders and dried forages can be especially rich. Intakes of natural OxBC for humans and livestock alike have been estimated. The exposure range for humans (1-22 mg/serving) is comparable to the safe intake of β-carotene (<15 mg/d). In livestock, OxBC in alfalfa can contribute ~550-850 mg/head/d for dairy cattle but in forage-deficient poultry feed much less (~1 ppm). Livestock intake of supplemental synthetic OxBC is comparable to OxBC potentially available from traditional plant sources. Human intake of synthetic OxBC in meat from livestock fed OxBC is similar to a single serving of food made with carrot powder. It is concluded that consumption of synthetic OxBC at levels comparable to natural OxBC is safe for humans and animals.
Topics: Animals; Cats; Cattle; Dietary Exposure; Dogs; Escherichia coli; Humans; Mice; Micronucleus Tests; Oxidation-Reduction; Poultry; Salmonella typhimurium; Swine; beta Carotene
PubMed: 33891992
DOI: 10.1016/j.fct.2021.112207 -
Molecules (Basel, Switzerland) Oct 2022β-cyclocitral (βCC), a main apocarotenoid of β-carotene, increases plants' resistance against stresses. It has recently appeared as a novel bioactive composite in a... (Review)
Review
β-cyclocitral (βCC), a main apocarotenoid of β-carotene, increases plants' resistance against stresses. It has recently appeared as a novel bioactive composite in a variety of organisms from plants to animals. In plants, βCC marked as stress signals that accrue under adverse ecological conditions. βCC regulates nuclear gene expression through several signaling pathways, leading to stress tolerance. In this review, an attempt has been made to summarize the recent findings of the potential role of βCC. We emphasize the βCC biosynthesis, signaling, and involvement in the regulation of abiotic stresses. From this review, it is clear that discussing compound has great potential against abiotic stress tolerance and be used as photosynthetic rate enhancer. In conclusion, this review establishes a significant reference base for future research.
Topics: beta Carotene; Plants; Diterpenes; Aldehydes; Stress, Physiological; Gene Expression Regulation, Plant
PubMed: 36296438
DOI: 10.3390/molecules27206845