8-OHdG (8-hydroxy-2'-deoxyguanosine)

When a hydroxyl radical hits guanine in DNA, the product is 8-oxo-guanine. Repair enzymes cut it out as 8-hydroxy-2'-deoxyguanosine and the kidney excretes it. Measuring it in urine gives a whole-body integral of oxidative DNA damage over the preceding hours, which is why it has become the standard oxidative-stress readout in occupational and clinical studies.

Melanie Graille, Nancy Hopf and colleagues screened 1,246 articles and pooled 84 of them, covering 129 study subgroups of healthy adults aged 18 and over, in a PROSPERO-registered meta-analysis. Method drives the number: chemical methods gave a pooled 3.9 ng/mg creatinine (IQR 3-5.5) in adults with mean BMI at or below 25, and 2.8 ng/mg creatinine (IQR 2.4-3.5) in those above 25. Immunological methods gave 9.0 ng/mg creatinine (IQR 5.9-19.8) and 7.7 ng/mg creatinine (IQR 5.8-10.9) for the same groups [1]. That is a two- to three-fold gap between assay families in the same population, which makes cross-study comparison hazardous. Reported Italian reference ranges are 3.25 to 6.85 ng/mg creatinine in women and 2.9 to 5.5 in men [1]. Smoking raised concentrations 2.84 fold in lean adults by chemical methods (95% CI 2.56-3.16, p < 0.0001) [1]. No gender effect was observed [1].

Damage rises with age. A Mayo Clinic study of 146 healthy adults aged 19 to 89 found relative 8-oxo-dG in people aged 65 to 80 was roughly 25% higher than in those aged 20 to 35, P < 0.01, while the related adduct 8-oxo-2dA did not change [2].

The disease association is clearest in cancer. Cheng Guo and colleagues compared 84 untreated, pathologically confirmed colorectal cancer patients with 142 healthy volunteers using UPLC-MS/MS. Urinary 8-OHdG averaged 1.68 plus or minus 0.85 nmol/mmol creatinine in patients against 1.07 plus or minus 0.49 in controls, with stage I cases already at 1.30 plus or minus 0.61 [3]. Note the different unit, nmol/mmol creatinine, another reason to read the method line before the number.

How it is measured: urine, ideally first-morning or 24-hour, normalised to creatinine, by ELISA or by mass spectrometry. Mass spectrometry is the reference method and reads systematically lower. Serum and leukocyte DNA measurements exist but are less standardised.

How to move it: coenzyme Q10 has the cleanest randomised evidence on the neighbouring lipid marker, lowering malondialdehyde with a standardised mean difference of -1.12 (95% CI -1.58 to -0.65, p < .0001) across 19 trials, alongside higher glutathione peroxidase (SMD 0.45, 95% CI 0.17-0.74, p = .002) [4]. Whether lowering an oxidative marker changes any hard outcome is still unanswered.