Homocysteine and cognition: A systematic review of 111 studies

Setién-Suero, Esther; Suárez-Pinilla, Marta; Suárez-Pinilla, Paula; Crespo‐Facorro, Benedicto; Ayesa-Arriola, Rosa

doi:10.1016/j.neubiorev.2016.08.014

Cited by 64 publications

(54 citation statements)

References 164 publications

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“…Epidemiological studies have reported the association between high circulating Hcy levels and AD, while longitudinal observations have revealed that the influence of Hcy on AD is independent from other confounders17181920. However, conflicting results have also been published regarding this relationship2122.…”

Section: Discussionmentioning

confidence: 99%

Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer’s phenotype

Barrero

Merali

et al. 2017

Sci Rep

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Environmental and genetic risk factors are implicated in the pathogenesis of Alzheimer’s disease (AD). However, how they interact and influence its pathogenesis remains to be investigated. High level of homocysteine (Hcy) is an AD risk factor and associates with an up-regulation of the ALOX5 gene. In the current paper we investigated whether this activation is responsible for the Hcy effect on the AD phenotype and the mechanisms involved. Triple transgenic mice were randomized to receive regular chow diet, a diet deficient in folate and B vitamins (Diet), which results in high Hcy, or the Diet plus zileuton, a specific ALOX5 inhibitor, for 7 months. Compared with controls, Diet-fed mice had a significant increase in Hcy levels, memory and learning deficits, up-regulation of the ALOX5 pathway, increased Aβ levels, tau phosphorylation, and synaptic pathology, which were absent in mice treated with zileuton. In vivo and vitro studies demonstrated that the mechanism responsible was the hypomethylation of the ALOX5 promoter. Our findings demonstrate that the up-regulation of the ALOX5 is responsible for the Hcy-dependent worsening of the AD phenotype in a relevant mouse model of the disease. The discovery of this previously unknown cross-talk between these two pathways could afford novel therapeutic opportunities for treating or halting AD.

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Section: Discussionmentioning

confidence: 99%

Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer’s phenotype

Barrero

Merali

et al. 2017

Sci Rep

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“…Nevertheless, our preliminary findings on Sulmedol on lowering Hcy levels in normal subjects, and in improving the neurobehavioral symptoms in moderateadvanced AD stage, raise the relevance of Sulmedol in targeting Hcy/ H 2 S link in development of novel AD therapeutics. Intervention trials using B-vitamin supplementation, however, have produced somewhat inconsistent findings on cognitive function [18][19][20][21][22]. In reviewing the plethora of many cross-sectional and prospective studies, increased levels of plasma total homocysteine are related to the severity of cognitive impairment and AD and vascular dementia.…”

Section: Discussionmentioning

confidence: 99%

“…By making use of a patented biotechnology for upscale manufacturing and quality control, the product has achieved a purity of 99.5% [18]. Pharmacokinetics data indicated that 10% to 40% of ingested sulfur is absorbed from the gastrointestinal tract as sulfides and excreted as sulfates in the urine.…”

Section: A Study Protocolmentioning

confidence: 99%

“…The relative risk of AD was 1.8 per increased of standard deviation (SD) at baseline. A recent meta-analysis of 111 pertinent studies [18] reveals a positive trend between cognitive decline and increased plasma Hcy levels in general population and in patients with cognitive impairments and Folstein Mini-Mental State scores (MMS). The threshold cut-off value of Hcy level for AD risk is set at 10.0 μmol/L.…”

Section: Introductionmentioning

confidence: 99%

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Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

Chiu¹,

Khan²,

Badmaev³

et al. 2017

J Syst Integr Neurosci

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Introduction: There is mounting evidence to suggest that hyper-homocysteinemia (eHct) correlates with cognitive decline severity and cortical atrophy in AD. Hydrogen Sulfide (H 2 S) exerts neuroprotection through regulating Homocysteine (eHcy) signaling. Elemental sulfur can mediate H 2 S neuroprotection through the trans-sulfuration pathway and correct the the dysregulation of H 2 S /Hct signaling in AD. Sublimed Sulfur, formulated as SULMEDOL and approved for the treatment of lactose intolerance, activates gut beta-galactosidase (GALAC). We repurpose Sulmedol from lactose intolerance to likely CNS effect, since gut GALAC cross-talks with senescence-related GALAC expression in the brain. In view of the known regulatory function of GALAC in CNS endosomal-lysosomal autophagy system , we propose that SULMEDOL may rescue aberrant autophagy in AD.

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“…It is logical that riboflavin would have an impact on cognitive function because homocysteine (Hcy) metabolism and one-carbon metabolism rely on it. Any reduction in the activity of enzymes in these pathways due to insufficient riboflavin, or other B vitamins, results in high Hcy, metabolic disorders, and accelerated brain cell death and is associated with cognitive decline, Alzheimer's disease, and Parkinson's disease (94)(95)(96)(97)(98)(99).…”

Section: Riboflavinmentioning

confidence: 99%

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Cereal Foods World

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Homocysteine and cognition: A systematic review of 111 studies

Abstract: Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.

Cited by 64 publications

References 164 publications

Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer’s phenotype

Five lipoxygenase hypomethylation mediates the homocysteine effect on Alzheimer’s phenotype

Exploratory study of sublimed sulfur, in cognitively normal subjects and in Alzheimer’s dementia (AD) subjects: implications for Sulfur targeting Hydrogen sulfide (H2S)/Homocysteine (Hcy) and beta-galactosidase (GALAC)/Autophagy Signaling in AD

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