The Impact of Supplemental Macular Carotenoids in Alzheimer's Disease: A Randomized Clinical Trial

Nolan, John M.; Loskutova, Ekaterina; Howard, Alan; Mulcahy, Ríona; Moran, Rachel; Stack, Jim; Bolger, Maggie; Coen, Robert F.; Dennison, Jessica; Akuffo, Kwadwo Owusu; Owens, Niamh; Power, Rebecca; Thurnham, David I.; Beatty, Stephen

doi:10.3233/jad-142265

Cited by 79 publications

(66 citation statements)

References 49 publications

(55 reference statements)

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“…Study design, subject recruitment, exclusion criteria, blood sample collection/serum preparation methods as well as baseline/six months carotenoid supplementation statistics for this patient cohort have been previously reported by Nolan et al(see [25], [26]). …”

Section: Methodsmentioning

confidence: 99%

“…They are lipid soluble, are transported principally by lipoproteins and can be broadly classified as either oxygenated xanthophylls or non-oxygenated carotenes [21]. Several authors have shown a significantly lower serum concentration of carotenoids (lutein, zeaxanthin and meso-zeaxanthin) in AD subjects [22], [23], [24] which can be increased after 6 months of supplementation with carotenoids [25].…”

Section: Introductionmentioning

confidence: 99%

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Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Ademowo

Dias

Milic

et al. 2017

Free Radical Biology and Medicine

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Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay.AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso-zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months.The MRM-MS method determined serum POVPC sensitively (from 10 µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003).In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Ademowo

Dias

Milic

et al. 2017

Free Radical Biology and Medicine

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“…Weekly intake of carotenoidrich foods (eggs, broccoli, corn, dark green leafy vegetables) was recorded using a dietary LZ screener previously used by our group and developed by Elizabeth Johnson. 33 …”

Section: Demographic Lifestyle Medical and Ophthalmic Assessmentmentioning

confidence: 99%

Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials – Report 1

Nolan

Power

Stringham

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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METHODS. Subjects consumed daily a formulation containing 10 mg L, 2 mg Z, and 10 mg MZ (active group; n ¼ 53) or placebo (n ¼ 52) for a period of 12 months. Study visits were at baseline, 3, 6, and 12 months. Contrast sensitivity at 6 cycles per degree (cpd) was the primary outcome measure (POM). Secondary outcome measures included CS at other spatial frequencies, best-corrected visual acuity (BCVA), glare disability, photostress recovery, and light scatter. Macular pigment optical density (MPOD) was measured using dual-wavelength autofluorescence, and serum carotenoid concentrations were analyzed using high performance liquid chromatography (HPLC).RESULTS. Compared to placebo, statistically significant improvements from baseline CS were detected at 6 (P ¼ 0.002) and 1.2 (P ¼ 0.004) cpd in the active group. Additionally, improvements in CS were commensurate with the observed increases in retinal concentrations of these carotenoids (r ¼ 0.342, P ¼ 0.002 at 6 cpd). CONCLUSIONS.These results indicate that dietary fortification with the macular carotenoids can have meaningful effects on visual function.

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“…This hypothesis is supported by many lines of investigation employing cell free models, culture systems and epidemiological approaches and clinical trials [3,47] , but sources of stress and types of antioxidants are numerous and the mechanisms whereby antioxidant protection can occur are also many. Of particular relevance to this study are prior investigations in which stress was induced using photic sources, and antioxidant supplementation included the use of macular xanthophylls, especially zeaxanthin, in combination with vitamin E. This combination of antioxidants has been previously shown to synergistically protect against photosensitized (RB-mediated) lipid peroxidation in liposomal model systems [62].…”

Section: Discussionmentioning

confidence: 99%

Zeaxanthin and α-tocopherol reduce the inhibitory effects of photodynamic stress on phagocytosis by ARPE-19 cells

Olchawa

Herrnreiter

Piłat

et al. 2015

Free Radical Biology and Medicine

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Zeaxanthin and α-tocopherol have been previously shown to efficiently protect liposomal membrane lipids against photosensitized peroxidation, and to protect cultured RPE cells against photodynamic killing. Here the protective action of combined zeaxanthin and α-tocopherol was analyzed in ARPE-19 cells subjected to photodynamic (PD) stress mediated by rose Bengal (RB) or merocyanine-540 (MC-540) at sub-lethal levels. Stress-induced cytotoxicity was analyzed by the MTT assay. The peroxidation of membrane lipids was determined by HPLC-EC(Hg) measurements of cholesterol hydroperoxides using cholesterol as a mechanistic reporter molecule. The specific phagocytosis of FITC-labeled photoreceptor outer segments (POS) isolated from bovine retinas was measured by flow cytometry, and the levels of phagocytosis receptor proteins αv integrin subunit, β5 integrin subunit and MerTK were quantified by Western blot analysis. Cytotoxicity measures confirmed that PD stress levels used for phagocytosis analysis were sub-lethal and that antioxidant supplementation protected against higher, lethal PD doses. Sub-lethal PD stress mediated by both photosensitizers induced the accumulation of 5α-OOH and 7α/β-OOH cholesterol hydroperoxides and the addition of the antioxidants substantially inhibited their accumulation. Antioxidant delivery prior to PD stress also reduced the inhibitory effect of stress on POS phagocytosis and partially reduced the stress-induced diminution of phagocytosis receptor proteins. The use of a novel model system where oxidative stress was induced at sub-lethal levels enable observations that would not be detectable using lethal stress models. Moreover, novel observations about the protective effects of zeaxanthin and α-tocopherol on photodynamic damage to ARPE-19 cell membranes and against reductions in the abundance of receptor proteins involved in POS phagocytosis, a process essential for photoreceptor survival, supports the importance of the antioxidants in protecting of the retina against photooxidative injury.

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The Impact of Supplemental Macular Carotenoids in Alzheimer's Disease: A Randomized Clinical Trial

Abstract: Supplementation with the macular carotenoids (MZ, Z, and L) benefits patients with AD, in terms of clinically meaningful improvements in visual function and in terms of MP augmentation.

Cited by 79 publications

References 49 publications

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials – Report 1

Zeaxanthin and α-tocopherol reduce the inhibitory effects of photodynamic stress on phagocytosis by ARPE-19 cells

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