Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta‐analysis

Silva, Sofia Lopes da; Vellas, Bruno; Elemans, Saskia; Luchsinger, José A.; Kamphuis, Patrick; Yaffe, Kristine; Sijben, John; Groenendijk, Martine; Stijnen, Theo

doi:10.1016/j.jalz.2013.05.1771

Cited by 273 publications

(209 citation statements)

References 129 publications

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“…Several candidates have been proposed to prevent or reduce oxidative damage, and have been investigated as treatments for AD (Table 3). Deficits in plasma levels of antioxidants are well documented in patients with AD [111,112,140]. Early research administering antioxidants for AD treatment focused on vitamins C and E. Both these vitamins are significantly reduced in the plasma of patients with AD [111].…”

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

“…Deficits in plasma levels of antioxidants are well documented in patients with AD [111,112,140]. Early research administering antioxidants for AD treatment focused on vitamins C and E. Both these vitamins are significantly reduced in the plasma of patients with AD [111]. Multiple preclinical studies on vitamin C and vitamin E using transgenic AD mouse models indicated decreased lipid peroxidation, memory deficits, and Aβ plaque burden [114][115][116].…”

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

“…A more recent randomized trial of vitamin E in veterans showed a 19 % delay in clinical progression per year [120]. In addition to vitamins C and E, several other antioxidant vitamins, including vitamins A, B 12 , and D, have been investigated owing to their deficient levels in patients with AD [111,113]. These vitamins failed to show significant efficacy when used in clinical settings (ClinicalTrials.gov identifier: NCT00235716), despite positive outcomes in preclinical models.…”

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

“…Nutraceuticals hold promise as effective modifiers of multifaceted cellular pathways that are defective in the prodromal state of AD. Numerous vitamins and natural compounds elicit effects on specific targets of the bioenergetic system in the brain; some micronutrients may offset the deficiencies often associated with early AD [111,112]. Natural compounds combined into a synergistic formulation could provide an effective nutraceutical-based mode of prevention for AD and other neurodegenerative disorders.…”

Section: Summary and Concluding Commentsmentioning

confidence: 99%

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Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

2015

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Alzheimer's disease (AD) has a complex and progressive neurodegenerative phenotype, with hypometabolism and impaired mitochondrial bioenergetics among the earliest pathogenic events. Bioenergetic deficits are well documented in preclinical models of mammalian aging and AD, emerge early in the prodromal phase of AD, and in those at risk for AD. This review discusses the importance of early therapeutic intervention during the prodromal stage that precedes irreversible degeneration in AD. Mechanisms of action for current mitochondrial and bioenergetic therapeutics for AD broadly fall into the following categories: 1) glucose metabolism and substrate supply; 2) mitochondrial enhancers to potentiate energy production; 3) antioxidants to scavenge reactive oxygen species and reduce oxidative damage; 4) candidates that target apoptotic and mitophagy pathways to either remove damaged mitochondria or prevent neuronal death. Thus far, mitochondrial therapeutic strategies have shown promise at the preclinical stage but have had little-to-no success in clinical trials. Lessons learned from preclinical and clinical therapeutic studies are discussed. Understanding the bioenergetic adaptations that occur during aging and AD led us to focus on a systems biology approach that targets the bioenergetic system rather than a single component of this system. Bioenergetic system-level therapeutics personalized to bioenergetic phenotype would target bioenergetic deficits across the prodromal and clinical stages to prevent and delay progression of AD.

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Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

Section: Oxidative Damage As a Therapeutic Targetmentioning

confidence: 99%

Section: Summary and Concluding Commentsmentioning

confidence: 99%

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Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

2015

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“…About 15% of Japanese with the TT genotype of MTHFR C677T require 400 μg/day of folate to increase the serum folate level to that of CC and CT genotypes. Folate deficiency among persons with dementia was confirmed by meta‐analysis of 31 studies (Lopes da Silva et al 2014) and of Japanese dementia studies (Kageyama et al 2008). The risk of brain infarction is 3.4‐fold higher in persons with the TT type compared to persons with the CC type (Morita et al 1998).…”

Section: Outline Of the Sakado Folate Projectmentioning

confidence: 92%

Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification

Kagawa

Hiraoka

Kageyama

et al. 2017

Congenital Anomalies

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The introduction of mandatory fortification of grains with folate in 1998 in the United States resulted in 767 fewer spina bifida cases annually and a cost saving of $603 million per year. However, far more significant medical cost savings result from preventing common diseases, including myocardial infarction, stroke, dementia and osteoporosis. A cost‐effectiveness analysis showed a gain of 266 649 quality‐adjusted life‐years and $3.6 billion saved annually, mainly due to the reduction of cardiac infarction. The recommended folate intake in Japan is 240 μg/day whereas it is 400 μg/day internationally. Our Sakado Folate Project targeted individuals with genetic polymorphism of methylenetetrahydrofolate reductase or with hyperhomocysteinemia. Using, for example, folate‐fortified rice, resulted in an increase in serum folate and a decrease in serum homocysteine in the participants, and reduced medical costs were achieved by decreasing myocardial infarction, stroke, dementia and fracture. Due to the small population of Sakado City (approximately 101 000) and small number of births (693) in 2015, a decrease in spina bifida could not be confirmed but there was a significant decrease in the number of very low birthweight infants. The genome notification of subjects was effective in motivating intake of folate, but the increase in serum folate (from 17.4 to 22.5 nmol/L, 129%) was less than that observed following compulsory folic acid fortification of cereals in the USA (from 12.1 to 30.2 nmol/L, 149.6%). Mandatory folic acid fortification is cheap in decreasing medical costs and is thus recommended in Japan.

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Omega 3 fatty acids for the treatment of dementia

Burckhardt¹,

Herke²,

Wustmann³

et al. 2015

Cochrane Database of Systematic Reviews

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Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta‐analysis

Cited by 273 publications

References 129 publications

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification

Omega 3 fatty acids for the treatment of dementia

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