Evidence map›Paper›PMID 21795440›Full record

Trial reportThe American journal of clinical nutrition2011

Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation.

Rajagopal V Sekhar, Sanjeet G Patel, Anuradha P Guthikonda, Marvin Reid, Ashok Balasubramanyam, George E Taffet, Farook Jahoor

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in The American journal of clinical nutrition, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02324426 (Central Nervous System Uptake of Intranasal Glutathione in Parkinson's Disease), which is not on this map. Cited by 159 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 1 pooled it
6.1field-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.

NCT02324426 phase1completednot on this mapstarted 2014, after this paper: background citation

Central Nervous System Uptake of Intranasal Glutathione in Parkinson's Disease

TypeinterventionalSponsorUniversity of WashingtonRan2014 to 2015Enrolled15ConditionsParkinson's DiseaseArmsReduced Glutathione
3 · Its place in the literature

Who cites it

159 citing papers in PubMed, 1 synthesis or guideline pooled it, 322 citations in OpenAlex.

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99 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Rajagopal V SekharTranslational Metabolism Unit, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.
Sanjeet G Patel
Anuradha P Guthikonda
Marvin Reid
Ashok Balasubramanyam
George E Taffet
Farook Jahoor
Baylor College of Medicine · US

Funding

ZOLENDRONIC ACID IN CHILDREN W/ SEVERE OSTEOGENESIS IMPERFECTAM01RR000188 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LOUIS, CHRYSTAL U · 1985 to 2011
$30.6M
TRAINING PROGRAM IN MOLECULAR ENDOCRINOLOGYT32DK007696 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI MOORE, DAVID D · 1993 to 2012
$2.8M
NCRR NIH HHS M01-RR00188NIDDK NIH HHS T32-DK07696
6 · The paper itself

Abstract

backgroundAging is associated with oxidative stress, but underlying mechanisms remain poorly understood.

objectiveWe tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in aging and whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress.

designEight elderly and 8 younger subjects received stable-isotope infusions of [2H(2)]glycine, after which red blood cell (RBC) glutathione synthesis and concentrations, plasma oxidative stress, and markers of oxidant damage (eg, F(2)-isoprostanes) were measured. Elderly subjects were restudied after 2 wk of glutathione precursor supplementation.

resultsCompared with younger control subjects, elderly subjects had markedly lower RBC concentrations of glycine (486.7 ± 28.3 compared with 218.0 ± 23.7 μmol/L; P < 0.01), cysteine (26.2 ± 1.4 compared with 19.8 ± 1.3 μmol/L; P < 0.05), and glutathione (2.08 ± 0.12 compared with 1.12 ± 0.18 mmol/L RBCs; P < 0.05); lower glutathione fractional (83.14 ± 6.43% compared with 45.80 ± 5.69%/d; P < 0.01) and absolute (1.73 ± 0.16 compared with 0.55 ± 0.12 mmol/L RBCs per day; P < 0.01) synthesis rates; and higher plasma oxidative stress (304 ± 16 compared with 346 ± 20 Carratelli units; P < 0.05) and plasma F(2)-isoprostanes (97.7 ± 8.3 compared with 136.3 ± 11.3 pg/mL; P < 0.05). Precursor supplementation in elderly subjects led to a 94.6% higher glutathione concentration, a 78.8% higher fractional synthesis rate, a 230.9% higher absolute synthesis rate, and significantly lower plasma oxidative stress and F(2)-isoprostanes. No differences in these measures were observed between younger subjects and supplemented elderly subjects.

conclusionsGlutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging.

Indexed as

Dietary SupplementsAdultAgedAge FactorsAgingCysteineErythrocytesF2-IsoprostanesGlutathioneGlycineHumansIsotopesMetabolic DiseasesOxidative StressStaining and LabelingCysteineF2-IsoprostanesGlutathioneGlycineIsotopes

Identifiers

PMID21795440
PMCPMC3155927
OpenAlexW2115817059

What OpenQuestion holds

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Registered trials

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 OpenQuestion graph.