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Review

Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis

1
Center for Primary Care and Public Health (Unisanté), University of Lausanne, Route de la Corniche, 21066 Epalinges-Lausanne, Switzerland
2
Institut national de recherche et de sécurité (INRS), 54000 Nancy, France
3
Swiss Center for Applied Human Toxicology (SCAHT), Missionsstrasse 64, 4055 Basel, Switzerland
*
Author to whom correspondence should be addressed.
Both are last authors.
Int. J. Mol. Sci. 2020, 21(11), 3743; https://doi.org/10.3390/ijms21113743
Received: 30 April 2020 / Revised: 21 May 2020 / Accepted: 22 May 2020 / Published: 26 May 2020
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)

Abstract

:
Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed.

1. Introduction

Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS), and an overproduction of ROS has negative consequences for cell physiology [1]. When ROS concentration is in excess, oxidative damage to proteins, lipids, and DNA occurs, thus causing structural and functional cellular changes. DNA damage is usually repaired primarily via the base excision repair pathway, and oxidized products are excreted in urine [2]. 8-hydroxy-2-deoxyguanosine (8-OHdG) is one of the most widely studied oxidized metabolites and is considered as a biomarker for oxidative damage of DNA [3,4]. The formation of 8-OHdG by oxygen radicals was first reported in 1984 by Kasai and Nishimura [5].
The interaction of the hydroxyl radical, the most important oxygen-free radical, with the nucleobases of the DNA strand, such as guanine, leads to the formation of 8-OHdG [6] (Figure 1).
Some diseases, such as cardiovascular or chronic obstructive pulmonary diseases (COPD), have been associated with excessive concentrations of 8-OHdG [7,8]. 8-OHdG levels also increase due to smoking, aging, or occupational exposure to physical, chemical, or biological substances [9,10].
A recent study suggested that 8-OHdG had high intraclass correlation coefficients (0.96), reproducible measurements, and low coefficients of variation and was the most suitable biomarker of oxidative stress in spot urine samples [11]. Concentrations of urinary oxidative stress biomarkers have been proposed as an effect biomarker to survey populations exposed to xenobiotics such as particulates, oxidizing agents, and lately, engineered nanomaterials [12,13].
Measuring urinary 8-OHdG has some advantages as it is very stable in urine [14], it is noninvasive, and its excretion is likely to reflect the oxidative DNA damage [15] and can be assessed by two main analytical techniques: mass-based methods (using either gas (GC) or liquid (LC) chromatography) and immunological methods. Another source of 8-OHdG in urine is DNA polymerase-dependent incorporation of 8-oxodGTP from the nucleotide pool [16]. Chromatographic methods are considered to be the gold standard; however, immunological techniques, which are less costly and time-consuming, are widely used because enzyme-linked immunosorbent assay (ELISA) kits have been developed for rapid detection and quantification of 8-OHdG [14,17].
A background range for 8-OHdG has been reported in different studies for healthy persons [11,18,19,20]. However, these studies reported a wider range of values, making the identification of background cut-off values challenging.
Therefore, the systematic review and meta-analyses of the reported values appears the most appropriate approach to bypass this issue. Our objective was to assess background ranges for urinary 8-OHdG concentrations in healthy adults.

2. Results

Chemical methods were used in 44 of the 128 study subgroups, and immunological techniques were used in 84 (Table 1). We decided to stratify the subgroups by body mass index (BMI), gender, and smoking status reported.

2.1. Descriptive Results

We retrieved 1246 articles, included 84 articles, and considered 129 study subgroups (Figure 2, Table 2, Table 3, Table 4 and Table 5) in the quantitative synthesis, which we stratified by main quantification techniques: immunological and chemical methods. For subgroups evaluated with the chemical methods, 31 studies had participants with a mean BMI between 18 and 25 (14 study subgroups of nonsmokers and 2 study subgroups of smokers) (Figure 3, Table 2). Nine studies had participants with a mean BMI > 25 (three study subgroups of nonsmokers and two study subgroups of smokers) (Figure 4, Table 3). The mean BMI was unknown for four study subgroups.
For subgroups analyzed with immunological techniques, 47 studies had participants with a mean BMI between 18 and 25 (24 study subgroups of nonsmokers, no study subgroups of smokers and 6 study subgroups with unknown smoking status) (Figure 5, Table 4). Twenty-six studies had participants with a mean BMI > 25 (13 study subgroups of nonsmokers and 6 study subgroups of smokers) (Figure 6, Table 5). The mean BMI was unknown for 11 study subgroups. Supplementary material provides detailed information on the criteria used for the quality assessment (S1) and on the quality level of each included study subgroup (S2). Overall, two study subgroups (1.8%) were classified as low quality, 66 (58.4%) as moderate quality, and 45 study subgroups (39.8%) were of high quality.

2.2. Meta-Analysis Results

As between-study heterogeneity was much larger than the between-subject heterogeneity, we decided to use a mixed model with study ID as a random effect. The IQR of subgroup-specific GM in subgroups with a mean BMI ≤ 25 with 8-OHdG measured using chemical methods was 3 to 5.5 ng/mg creatinine (Table 1). IQR of subgroup-specific GM in subgroups with a mean BMI > 25 measured using immunological methods was 5.9 to 19.8 ng/mg creatinine (Table 1).
We compared urinary 8-OHdG concentrations by smoking status within the study subgroups analyzed with chemical techniques and found that for study subgroups with mean BMI ≤ 25, smokers were 2.84 ([2.56, 3.16], p < 0.0001) times greater compared to nonsmoker study subgroups.
For study subgroups with mean BMI > 25, smokers were 1.61 ([1.17, 2.23], p = 0.004) times greater compared to the nonsmoker study.
No consistent effects of BMI and gender were observed in our mixed model either for chemical or immunological methods. Gender and BMI seem to not influence urinary 8-OHdG concentrations.

3. Discussion

3.1. Interpretation of Findings

We found that urinary 8-OHdG concentrations in smokers were greater than in nonsmokers when analysis was conducted with chemical techniques. However, in the population with mean BMI between 18 and 25, this finding was mainly due to one study [32] and needs to be confirmed. The absence of BMI effect on 8-OHdG in urine is in line with data from Lee et al. 2010 [93].
The IQR range for 8-OHdG in urine given in this meta-analysis is in line with two other studies trying to define reference values for the Italian population (female: 3.25–6.85 ng/mg creatinine; male: 2.9–5.5 ng/mg creatinine) [94]. The absence of gender effect observed for 8-OHdG in this study is in line with data from the Italian population [94] but in contradiction with two others [93,95].
The analysis of the data was difficult due to the diversity in study design, analytical methods (chemical or immunoassay techniques), statistical analysis, and data presentation in studies included.

3.2. Quantification of 8-OHdG

The heterogeneity in techniques used to quantify urinary 8-OHdG makes it more difficult to compare data between laboratories.
Chemical techniques are superior to immunological techniques due to their sensitivity and specificity [14,96]. Chemical techniques require expensive instruments and trained users, but we recommend using chemical quantification methods as standard methods for future studies of biomonitoring.

3.3. Lack of Homogeneity in Data Collection and Reporting

Most studies used spot urine samples for 8-OHdG rather than 12- or 24-h collection. However, 8-OHdG levels showed fluctuation during the day under oxidative states [97], but good correlations have been observed between levels of 8-OHdG in spot morning urine and levels of 8-OHdG in the 24-h urinary collection [14]. Therefore, we included studies reporting spot morning urine, 12- or 24-h urinary samples. The first morning urine void is particularly valuable because it provides a time average for biomarker concentrations that may occur during the hours of sleep (approximately 8 h) and is also relatively free of dietary, physical, and environmental exposures [15]. A significant increase in time in the urinary 8-OHdG during the first part of the day was recently reported among smokers [15]. To make it easier to compare results between studies, we recommend collecting spot morning urine.

3.4. Limitations

We confirm that smokers have a significantly greater concentration of urinary 8-OHdG, as has been previously reported in the literature. The concentration differences need to be quantified, but with only a few studies in smokers available, this cannot be done at the present time.
We emphasize here that the values we report are for a healthy population. We were not able to analyze parameters previously reported to influence 8-OHdG concentrations such as occupation, pregnancy, special diet, vitamin, and physical activity due to the limited number of studies with such data.

3.5. Recommendations

The fluctuation in urine flow rate could in fact affect the assessment of urinary 8-OHdG. The urinary 8-OHdG concentrations need to be normalized by urinary creatinine concentrations for healthy adults. Different studies indicated a correlation between excretion of creatinine and 8-OHdG [94,95]. In addition, normalization with creatinine for spot urine can be considered as a surrogate for the 24-h excretion of 8-OHdG [94,98].
To reach consensual background of urinary 8-OHdG values, harmonization of the unit (ng/mg creatinine) is needed. Harmonization of the statistical reporting of the results is also recommended (geometric means (GM) and geometric standard deviations (GSD)). We suggest reporting the median and the 1st and 3rd quartile as GSDs are not easy to interpret.

4. Materials and Methods

We established a standardized protocol for systematic review and meta-analysis for a set of biomarkers of oxidative stress. This protocol was registered in the International Prospective Register of Systematic Reviews (registration number CRD 42020146623) [99] and described in detail by Hemmendinger et al. [100]. The protocol was then adapted for each biomarker depending on the biological matrix focused, here the urinary 8-OHdG. The methods and results of this study are reported following recommendations from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations [101,102].

4.1. Literature Search

The search strategy was done with a medical librarian. The MeSH (Medical Subject Headings) terms from the PubMed database and free text words were combined. The complete search string was: (“Smoking/urine”[Mesh] OR “Urine”[Mesh] OR Urine*[tiab] OR Urinary[tiab] OR Urinal*[tiab]) AND (“8-oxo-7-hydrodeoxyguanosine”[Supplementary Concept] OR 8-OHdg[tw] OR 8ohdg[tw] OR 8-oh-dg[tw] OR 8-ohg[tw] OR 8-OH-2dG[tw] OR 8-hydroxydeoxyguanosine[tw] OR 8-hydroxyguanine[tw] OR 8-hydroxy-g[tw] OR 8-hydroxy-dg[tw] OR 8-hydroxy-guanine[tw] OR 8-hydroxy-2-deoxyguanosine[tw]) NOT ((“Child”[Mesh] OR “Infant”[Mesh] OR “Adolescent”[MeSH]) NOT “adult”[MeSH]) NOT (animals[mh] NOT humans[mh]).

4.2. Study Selection

The search was performed on 7 May 2019. Rayyan [103], a systematic review web application, was used for title and abstract screening. We selected the studies in a stepwise process as depicted in Figure 6. To be included in the analysis, a study had to be in English and to provide urinary 8-OHdG concentrations in healthy adults (ages 18—no upper age limit) populations. We excluded non-human studies, in vitro studies, reviews, letters, expert opinions, and editorials. We read the eligible articles in depth, and only studies with original data from healthy (no known disease) adult populations were included in the statistical analysis. All techniques used for the quantification of 8-OHdG were included and classified accordingly. We excluded studies with coefficient variation <10% or >200%. We also excluded data suspected to have unit or reported value mistakes (more than three orders of magnitude higher than the median levels).

4.3. Data Extraction

We extracted the following information: first author name, publication year, study type, country, analytic method, sample time, sample size, gender, mean age, mean BMI, smoking status, season, occupation, pregnancy, diet, vitamin, exercise, outcome (8-OHdG concentration), references, and article DOI. We extracted all subgroup-specific data when data on several subgroups were available in a given paper. Then, we excluded all subgroups selected based on disease status (e.g., cardiovascular disease) and all subgroups selected based on an exposure status (e.g., bus drivers). If data on the same subgroup were reported for different times (e.g., different seasons), only the data at the time of participant inclusion were included. In a third round, we excluded duplicate data (e.g., control population reported in more than one study) and retained the most complete and the most recent study.

4.4. Statistical Analysis

First, we analyzed the values of urinary 8-OHdG measured in original studies in view of establishing the background ranges using meta-analysis. Measured values were generally log-normally distributed. We therefore computed geometric means (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis or equivalently m u L = ln ( G M ) and s d L = ln ( G S D ) . Further details on the data treatment and analyses are available elsewhere [104].
We could not compute standard errors on the geometric (or arithmetic) scale when neither standard deviation (SD), GSD, IQR, nor confidence interval (CI) were reported. As a consequence, we excluded these studies from the meta-analysis. We converted all the concentration values to the same units (ng/mg creatinine) before computing GM and GSD. We used 113.12 g/mol for the molecular weight for creatinine and 283.24 g/mol for 8-OHdG. We regrouped the data according to analytical techniques used; immunological techniques and chemical techniques. The data were analyzed separately.
We followed standard practice in meta-analysis [105] and represent the data as forest plots including the I-squared. This is an estimate of the between-study heterogeneity in percentage. If the between-study heterogeneity is much larger than the between-subject heterogeneity, then I2 is large. In this case, any attempt of obtaining a background value for individual participants will not be valid. In our case, a mixed model with study ID as a random effect is a more relevant analysis model. This yields results on the study subgroup level rather than at the individual level. Data management and statistical analyses were performed in STATA version 16 software.

5. Conclusions

We report pooled GM values for urinary 8-OHdG in healthy adults, separately for chemical and immunological methods. We observed a significant positive association between smoking status and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was shown. Urinary 8-OHdG can potentially be used to quantify excess oxidative stress due to external exposures when background values have been established in different populations. We recommend adjusting urine samples with creatinine, quantifying 8-OHdG with chemical methods, and reporting results as median and quartiles. Comparing values across studies will then be feasible.

Supplementary Materials

Supplementary Materials can be found at https://www.mdpi.com/1422-0067/21/11/3743/s1.

Author Contributions

I.G.C. and N.B.H. conceived the project, developed the necessary tools, and managed funding acquisition; M.H. and M.G. wrote the study protocol and implemented the literature search; M.G. and N.B.H. performed the screening for study selection, the systematic review, and data extraction; J.-J.S. performed data conversion and validation; P.W. realized statistical analysis; M.G. wrote the manuscript, which was further amended by all authors. All authors have read and agreed to the published version of the manuscript.

Funding

This study was conducted within the framework of EU Life Project “NanoExplore” (Grant N° LIFE17 ENV/GR/000285) and Franco-Swiss project “ROBoCoP” (Swiss National Science Foundation Grant N° IZCOZ0_177067).

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

8-OHdG8-hydroxy-2-deoxyguanosine
ROSReactive oxygen species
GMGeometric mean
GSDGeometric standard deviation
BMIBody mass index
SDStandard deviation
SEMStandard error of the mean
CVCoefficient of variation
IQRInterquartile range

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Figure 1. Structure of 8-OHdG.
Figure 1. Structure of 8-OHdG.
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Figure 2. Flow chart of study selection.
Figure 2. Flow chart of study selection.
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Figure 3. Forest plot of urinary 8-OHdG concentrations (ng/mg creatinine) measured with chemical techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
Figure 3. Forest plot of urinary 8-OHdG concentrations (ng/mg creatinine) measured with chemical techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
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Figure 4. Forest plot of urinary 8-OHdG levels (ng/mg creatinine) measured with chemical techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants
Figure 4. Forest plot of urinary 8-OHdG levels (ng/mg creatinine) measured with chemical techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants
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Figure 5. Forest plot of urinary 8-OHdG concentrations (ng/mg creatinine) measured with immunological techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
Figure 5. Forest plot of urinary 8-OHdG concentrations (ng/mg creatinine) measured with immunological techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
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Figure 6. Forest plot of urinary 8-OHdG concentrations (ng/mg creatinine) measured with immunological techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants.
Figure 6. Forest plot of urinary 8-OHdG concentrations (ng/mg creatinine) measured with immunological techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants.
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Table 1. Summary of geometric mean urinary 8-OHdG concentrations (ng/mg creatinine) in subgroups of healthy adult (18+ years) participants.
Table 1. Summary of geometric mean urinary 8-OHdG concentrations (ng/mg creatinine) in subgroups of healthy adult (18+ years) participants.
BMI ≤ 25BMI > 25
Analytical TechniquesAll ParticipantsSmoking Status All ParticipantsSmoking Status
Chemical3.9 *
(3–5.5)
(n ** = 31)
Nonsmokers 4.32.8
(2.4–3.5)
(n = 9)
Nonsmokers2.5
(n = 14)(2.9–5.5)(n = 3)(1.9–2.8)
Smokers22.2Smokers4.0
(n = 2)(3–41.4)(n = 2)(3.5–4.5)
Immunological9.0
(5.9–19.8)
(n = 47)
Nonsmokers11.57.7
(5.8 – 10.9)
(n = 26)
Nonsmokers9.3
(n = 24)(5.9–21.6)(n = 13)(7.8–14.7)
SmokersNASmokers6.0
(n = 0) (n = 6)(5.4–7)
* Median (IQR: 25%–75%); ** Number of included study subgroups; NA: Not Available.
Table 2. References for urinary 8-OHdG concentrations and computed GM (ng/mg creatinine) measured with chemical techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
Table 2. References for urinary 8-OHdG concentrations and computed GM (ng/mg creatinine) measured with chemical techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
ReferenceStudy GroupAnalytic MethodSampleCountrySample SizeMean AgeFemaleMaleSmoking StatusMean BMIAMGMIQRRangeMedianCIUnits
(8-OHdG/Creatinine)
Computed GM (ng/mg Creatinine)GSD
[21]Control groupHPLCspot urineChina49742.4811338450%23.724.47 ± 1.26 * nmol/mmol 111
[22]Control groupHPLC-MS/MSspot urineChina10631.62010652.8%23.793 ± 1.08 * μg/g 31
[23]Selenium group baseline valueHPLC with EC detectionspot urineUSA1730.70170%24.23.16 ± 1.28 * ng/mg31
[24]Baseline valueUPLC-MS-MS in positive EI modespot urineBelgium484034531.2%24.210.76 ± 2.83 * 7.05–20.92 μg/g 101
[25]Men baselineHPLCspot urineJapan237060.70237024.9%23.6 3.7 ± 1.6 * ng/mg 42
[25]Women baselineHPLCspot urineJapan405260.2405204.7%22.2 4.1 ± 1.7 * ng/mg 42
[26]Baseline valueLC-MS/MSspot urineTaiwan5823.8405851.7%24.55 2.63–11.54 4.42 µg/g 162
[27]Service staff groupHPLCspot urineChina6724.80670%23.2 1.40.9–1.8μmol/mol 23
[28]All populationHPLCspot urineJapan50342.420929427.4%22.5 2.37–4.030.8–10.03.01 μg/g 31
[29]Baseline valueHPLCspot urineKorea1025510200%24.16.5 ± 3.9 * μg/g 62
[30]Control groupHPLCspot urineJapan80540.3080546.7%23.73.79 ± 1.44 * ng/mg 41
[31]Baseline valueGC-MSspot urineSingapore2422.8NANA0%21.62.02 ± 1.12 * µmol/mol 52
[32]Non smoker group baselineHPLC with EC detection24 h urineChina3021.50300%22.86.3 ± 0.5 ** µmol/mol 142
[32]Smoker group baselineHPLC with EC detection24 h urineChina6021.8060100%22.618 ± 1 ** µmol/mol412
[33]Participants without strokeLC–MS/MSspot urineTaiwan13164.9577450%22.9 8.3–22.8 13 μg/g 132
[34]Male baselineHPLC-ECspot urineJapan7947.90790%22.32.81 ± 1.07 * μg/g32
[34]Female baselineHPLC-ECspot urineJapan1646.71600%20.63.04 ± 1.42 * μg/g 31
[35]Women baselineHPLCspot urineJapan3728–573705.4%21.5 3.2–5.2 3.9 μg/g 41
[35]Non smoking men group baselineHPLCspot urineJapan8728–570870%24.2 2.9–4.7 3.6 μg/g 41
[36]Baseline valueHPLC with an EC detectorspot urineJapan2346.81112100%23.6 3.02 2.24–4.07ng/mg51
[37]Control groupLC–MS/MSspot urineTaiwan12534.101250%22.8 4.1 ± 2.1 * μg/g 42
[38]Control groupHPLC-MS/MSspot urineChina18540.4124610%24.4 5.5 ± 2.2 * µg/g 62
[39]Control groupLC ECspot urineIndia13541.3101350%22.383.57 ± 0.63 * μmol/mol 91
[40]All populationHPLCspot urineJapan651760.34064245312.6%22.7 3.9 ± 1.6 * ng/mg 42
[41]Placebo group end of studyLC-MS/MSspot urineUSA1269660%252 ± 0.2 ** µmol/mol 51
[41]Tart cherryjuice group end of studyLC-MS/MSspot urineUSA1269660%251.8 ± 0.1 ** µmol/mol 41
[42]Male groupLC-MS/MSspot urineChina6937.8306943.5%24.14.55 ± 4.44 * μg/g 32
[42]Female groupLC-MS/MSspot urineChina2338.552300%22.14.34 ± 3.85 * μg/g 32
[43]Control groupLC–MS/MSspot urineTaiwan12951.7399027.9%24.64.3 ± 0.5 ** ng/mg 33
[44]Men groupHPLCspot urineJapan19644.4019643.9%23.83.3 ± 1.1 * µg/g 31
[44]Women groupHPLCspot urineJapan13640.413602.9%213.3 ± 1.1 * µg/g 31
* SD, ** SEM.
Table 3. References for urinary 8-OHdG concentrations measured and computed GM (ng/mg creatinine) with chemical techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants.
Table 3. References for urinary 8-OHdG concentrations measured and computed GM (ng/mg creatinine) with chemical techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants.
ReferenceStudy GroupAnalytic MethodSampleCountrySample SizeMean AgeFemaleMaleSmoking StatusMean BMIAMIQRMedianUnits
(8-OHdG/Creatinine)
Computed GM
(ng/mg Creatinine)
GSD
[45]Elderly low expose groupLC–MS/MSspot urineTaiwan7166.3636359.9%26.363.16 ± 4.07 * μg/g32
[23]Placebo groupHPLC with EC detectionspot urineUSA1931.10190%25.24.18 ± 4.78 * ng/mg32
[46]Control groupLC/MS/MSspot urineTaiwan16843.2NANA34%26.410.61 ± 7.77 * µmol/mol 212
[47]Control groupHPLCspot urineChina3138.703119.4%≤24 38.7%
>24 61.3%
1.0–4.01.3µmol/mol33
[48]Control non smoker groupHPLC–ECDspot urineTurkey1954.83160%29.12.1 ± 1 * μg/g21
[48]Control ex-smoker groupHPLC–ECDspot urineTurkey2157.53180%27.22.6 ± 0.8 * μg/g22
[48]Control smoker groupHPLC– ECDspot urineTurkey2451.1420100%26.54.2 ± 2.8 * μg/g32
[35]Smoking men group baselineHPLCspot urineJapan4028–57040100%25.1 3.6–5.64.5μg/g41
[49]Control group baselineHPLCspot urineUSA203920050%292.8 ± 1.7 * µg/g22
* SD.
Table 4. References for urinary 8-OHdG concentrations measured and computed GM (ng/mg creatinine) with immunological techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
Table 4. References for urinary 8-OHdG concentrations measured and computed GM (ng/mg creatinine) with immunological techniques in healthy (mean BMI ≤ 25 and no known disease), adult (18+ years) participants.
ReferenceStudy GroupSampleCountrySample SizeMean AgeFemaleMaleSmoking StatusMean BMIAMGMIQRRangeMedianCIUnits (8-OHdG/Creatinine)Computed GM (ng/mg Creatinine)GSD
[50]Healthy control group24 h urineThailand3041.431911NA22.564.32 ± 4.93 * μg/g32
[51]Healthy control group24 h urineThailand3041.431911NA22.565.27 ± 2.77 * μg/g52
[52]Control groupspot urineChina356015200%22.911.9 ± 4.9 * ng/mg111
[53]Control groupspot urineKorea41664.49232428.1%23.7 5.06 4.55–5.62μg/g52
[54]Control group spot urineKorea14068.83210865.5%22.46 4.88 4.43–5.38μg/g51
[55]Healthy young group24 h urineCanada1222.80120%255333 ± 1191 * ng/g51
[56]Apple group final valuespot urineChina1362.83100%24.2824.41 ± 343.66 * ng/mmol71
[56]Pomegranate group final valuespot urineChina1364.13100%23651.57 ± 332.44 * ng/mmol52
[57]placebo group baseline valuespot urineChina15051.58925841.3%23.8 60.89 ± 1.62* 58.19 ng/mg612
[57]Baseline line value Low FA groupspot urineChina14548.9875833.8%24.5 55.48 ± 1.74 * 53.51 ng/mg552
[57]Baseline value high FA groupspot urineChina14348.66944930.1%24.6 55.81 ± 1.72 * 54.73 ng/mg562
[58]Control group24 h urineJapan1540690%23.29.7 ± 4.6 * ng/mg92
[59]Control group Ispot urineChina2025.551730%19.7410.68 ± 1.07 ** ng/mg102
[59]Control group IIspot urineChina2024.51550%20.0911.96 ± 0.73 ** ng/mg121
[60]Male groupspot urineJapan19541.7019549.7%23.69.35 ± 3.66 * ng/mg91
[60]Female groupspot urineJapan19441.7194029.9%22.110.97 ± 5 * ng/mg102
[61]Non MS groupspot urineJapan63840.838525327.3%22.39.28 ± 4.15 * ng/mg82
[62]Male control spot urinePakistan3439.70340%19.8524.5 ± 6.6 * 11.08–33.8525.72 ng/mg261
[62]Female controlspot urinePakistan3239.523200%20.8324.5 ± 6.33 * 11.1–33.8524.47 ng/mg241
[63]Control groupspot urinePakistan3439.70340%20.924 ± 4 * 9–3025 ng/mg251
[64]Control groupspot urinePakistan34370340%20.825.8 ± 7 * 9.1–33.927.9 ng/mg281
[65]Pregnant womenspot urineKorea26129.626100%2120.8 ± 14.2 * µg/g172
[66]Control group baselinespot urineUK3231.715170%22.421.6 ± 12.6 * ng/mg192
[66]Test group baselinespot urineUK3231.715170%22.424 ± 13.3 * ng/mg212
[67]Control groupspot urineTurkey2040.71010NA22.527.84 ± 7.04 * ng/mg62
[68]Control groupspot urineJapan108230108NA22.510.4 ± 3.2 * ng/mg101
[69]Non exposed groupspot urineIran4335.5804321%19–2454.16 ± 26.98 * ng/mg482
[70]Control groupspot urineJapan5262.427250%248.8 ± 0.5 ** ng/mg81
[71]Male groupspot urineJapan27642.10276NA23.88.8 ± 0.2 ** ng/mg81
[71]Female groupspot urineJapan44542.74450NA21.99.8 ± 0.2 ** ng/mg92
[72]Male healthy populationspot urineJapan14243.6014231%22.411.5 ± 5.2 * ng/mg102
[72]Female healthy populationspot urineJapan13643.4136052.2%23.89.4 ± 3.4 * ng/mg91
[73]Control groupspot urineUSA4332.64300%23.26.31 ± 2.49 * ng/mg61
[74]Male groupspot urineJapan32342032342.7%23.78.85 ± 3.29 ng/mg81
[74]Female groupspot urineJapan44342.7443013.5%21.99.89 ± 4.54 * ng/mg92
[75]Green tea catechin-no exercise group baseline valuespot urineJapan822.4080%>18 <2515.9 ± 3.6 * ng/mg161
[75]Green tea catechin-exercise group baseline valuespot urineJapan821.1080%>18 <2522.9 ± 7.9 * ng/mg221
[75]Placebo groupspot urineJapan821.1080%>18 <2518 ± 6.2 * ng/mg171
[76]Men groupspot urineJapan27243.5027260.7%23.78.86 ± 3.36 * 2.13–21.87 μg/g81
[76]Women groupspot urineJapan29540.3295015.6%21.79.25 ± 4.03 * 0.05–25.56 μg/g82
[77]Baseline value 50km groupspot urineItaly641.83NANA0%21.084.38 ± 1.16 * ng/mg41
[78]Summer Non heating seasonspot urineChina3447.93400%23.212.7 ± 4.7 * 2.60, 25.813.6 ng/mg92
[79]Healthy volunteers Young groupspot urineTurkey3041.62280%22.13.24 ± 1.54 * ng/mg32
[79]Healthy volunteers Elderly groupspot urineTurkey3069.120100%23.65.74 ± 2.68 * ng/mg52
[80]Baseline valuespot urineChina2520.912130%20.673765.63 ± 958.14 * ng/mmol321
[15]Women group spot urineItaly333033029%20.7 3.68–7.20 5.21 ng/mg42
[81]Non exposed groupspot urineChina14327.89100438%21.0317.36 ± 13.5 * ng/mg142
* SD; ** SEM.
Table 5. References for urinary 8-OHdG concentrations measured and computed GM (ng/mg creatinine) with immunological techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants.
Table 5. References for urinary 8-OHdG concentrations measured and computed GM (ng/mg creatinine) with immunological techniques in healthy (mean BMI > 25 and no known disease), adult (18+ years) participants.
ReferenceStudy GroupSampleCountrySample SizeMean AgeFemaleMaleSmoking StatusMeanBMIAMIQRRangeMedianUnits (8-OHdG/Creatinine)Computed GM (ng/mg Creatinine)GSD
[82]Cocorit communitiesspot urineMexico1045.95530%278.2 ± 4.3 * μg/g72
[82]Pueblo Yaqui communitiesspot urineMexico1535.3967%26.75.7 ± 2.9 * μg/g52
[82]Campo 47spot urineMexico1539.510540%29.85.7 ± 3.3 * μg/g52
[83]Control groupspot urineUK6128.46109%2639.83 ± 2.92 ** ng/mg352
[55]Healthy older group24 h urineCanada1271.80120%28.87714 ± 1402 * ng/g81
[84]Water group baseline valuespot urineUSA4218–793210100%25.98.7 ± 1.3 ** ng/mg53
[84]Green tea group baseline valuespot urineUSA3518–79278100%26.510.8 ± 1.3 ** ng/mg92
[84]Black tea baseline valuespot urineUSA4318–793112100%26.79.5 ± 2.1 ** ng/mg62
[85]Water group baseline valuespot urineUSA4549.83213100%26.99.5 ± 1.3 ** ng/mg63
[85]Black tea baseline valuespot urineUSA4652.13412100%27.210.8 ± 2.5 ** ng/mg72
[85]Green tea group baseline valuespot urineUSA4251.63210100%27.28.7 ± 1.8 ** ng/mg53
[86]Placebo group baseline value24 h urineUSA4758.123240%28.917.6 ± 10.4 * ng/mg152
[86]Vit C group baseline value24 h urineUSA4661.226200%28.719.3 ± 9.3 * ng/mg172
[86]Vit E group baseline value24 h urineUSA4555.529160%28.616.5 ± 8.4 * ng/mg152
[86]Vit C + Vit E baseline value24 h urineUSA4657.724220%28.917.7 ± 9.5 * ng/mg162
[87]Control group24 h urineFinland10065465418%27.724.3 ± 15.2 * ng/mg212
[88]Control groupspot urineTaiwan274902755.6%25.85 ± 4.92 * µg/g42
[89]All populationspot urineJapan905260300%25.2 5.8–23.20.90–48.09.3ng/mg93
[90]Baseline valuespot urineCanada2868.5NANA0%27.110783 ± 5856 * ng/g92
[91]control group baselinespot urineSpain2330.422300%25.329.29 ± 0.69 ** ng/mg91
[91]DHA group baselinespot urineSpain2329.972300%25.629.81 ± 0.79 ** ng/mg91
[92]Placebo group men 24 h urineCanada874.8080%25.98329 ± 3032 * ng/g81
[92]Placebo group women 24 h urineCanada1068.31000%25.211622 ± 4379 * ng/g71
[92]Intervention group men baseline 24 h urineCanada1171.80110%27.87245 ± 2703 * ng/g111
[92]Intervention group women baseline 24 h urineCanada1069.51000%25.57942 ± 3071 * ng/g71
[15]Men group early morningspot urineItaly223402238.1%25.3 2.76–5.25 3.76ng/mg52
* SD; ** SEM.

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MDPI and ACS Style

Graille, M.; Wild, P.; Sauvain, J.-J.; Hemmendinger, M.; Guseva Canu, I.; Hopf, N.B. Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis. Int. J. Mol. Sci. 2020, 21, 3743. https://doi.org/10.3390/ijms21113743

AMA Style

Graille M, Wild P, Sauvain J-J, Hemmendinger M, Guseva Canu I, Hopf NB. Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis. International Journal of Molecular Sciences. 2020; 21(11):3743. https://doi.org/10.3390/ijms21113743

Chicago/Turabian Style

Graille, Melanie, Pascal Wild, Jean-Jacques Sauvain, Maud Hemmendinger, Irina Guseva Canu, and Nancy B. Hopf. 2020. "Urinary 8-OHdG as a Biomarker for Oxidative Stress: A Systematic Literature Review and Meta-Analysis" International Journal of Molecular Sciences 21, no. 11: 3743. https://doi.org/10.3390/ijms21113743

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