Evidence map›Paper›PMID 36774227›Full record

ReviewThe American journal of clinical nutrition2023

Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?

Richard J Johnson, Dean R Tolan, Dale Bredesen, Maria Nagel, Laura G Sánchez-Lozada, Mehdi Fini, Scott Burtis, Miguel A Lanaspa, David Perlmutter

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The American journal of clinical nutrition, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

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  18. The fructose survival hypothesis for obesity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Richard J JohnsonDepartment of Medicine, Rocky Mountain VA Medical Center, Aurora, CO, USA; Department of Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA. Electronic address: Richard.johnson@cuanschutz.edu.
Dean R TolanBiology Department, Boston University, Boston, MA, USA.
Dale BredesenDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Maria NagelDepartment of Neurology, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
Laura G Sánchez-LozadaDepartment of Cardio-Renal Physiopathology, National Institute of Cardiology Ignacio Chávez, Mexico City, Mexico.
Mehdi FiniDepartment of Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
Scott BurtisBurtis Chiropractic Center, Fairmont, MN, USA.
Miguel A LanaspaDepartment of Medicine, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
David PerlmutterUniversity of Miami Miller School of Medicine, Miami, FL, USA.
University of Colorado Anschutz Medical Campus · USBoston University · USInstituto Nacional de Cardiología · MXUniversity of California, Los Angeles · USUniversity of Miami · US

Funding

Scientific CoreP01AG032958 · NIA · UNIVERSITY OF COLORADO DENVER · PI RANDALL J. COHRS · 2022 to 2023
$8.8M
PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · UNIVERSITY OF COLORADO DENVER · 1995 to 2025
$7.7M
BLRD VA I01 BX004511NIA NIH HHS P01 AG032958NIDDK NIH HHS P30 DK048520NIDDK NIH HHS R01 DK121496
6 · The paper itself

Abstract

An important aspect of survival is to assure enough food, water, and oxygen. Here, we describe a recently discovered response that favors survival in times of scarcity, and it is initiated by either ingestion or production of fructose. Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain. How this survival mechanism affects brain metabolism, which in a resting human amounts to 20% of the overall energy demand, is only beginning to be understood. Here, we review and extend a previous hypothesis that this survival mechanism has a major role in the development of Alzheimer's disease and may account for many of the early features, including cerebral glucose hypometabolism, mitochondrial dysfunction, and neuroinflammation. We propose that the pathway can be engaged in multiple ways, including diets high in sugar, high glycemic carbohydrates, and salt. In summary, we propose that Alzheimer's disease may be the consequence of a maladaptation to an evolutionary-based survival pathway and what had served to enhance survival acutely becomes injurious when engaged for extensive periods. Although more studies are needed on the role of fructose metabolism and its metabolite, uric acid, in Alzheimer's disease, we suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine whether there is potential benefit in the prevention, management, or treatment of this disease.

Indexed as

Alzheimer DiseaseInsulin ResistanceFructoseGlucoseHumansUric AcidFructoseGlucoseUric AcidAlzheimer’s diseaseenergy metabolismfructoseinsulin resistancemetabolic syndrome

Identifiers

PMID36774227
PMCPMC10196606
OpenAlexW4315434906

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.