Oxidative stress results from an imbalance between oxidants and antioxidants that leads to cellular damage. Oxidative stress is complex, involving both intrinsic and extrinsic factors. It is closely tied to inflammation and contributes to aging, cancer and cardiovascular disease. As mentioned in a previous blog post Redox Redux, oxidative stress and damage are challenging to measure directly.

Researchers are now starting to use an ‘Oxidative Balance Score’ (OBS) to assess the impacts of oxidants and anti-oxidants on individuals. The score is calculated using a combination of 14 dietary and lifestyle components, selected based on their relationship to oxidative stress. They include ten antioxidants: total vitamin C, α-carotene, total β–carotene, β-cryptoxanthin, total vitamin E, lutein, lycopene and selenium consumed in the diet, as well as aspirin and nonsteroidal anti-inflammatory drug use. These are balanced against four oxidants: consumption of polyunsaturated fatty acids, total iron intake (from red meat), a history of smoking, and alcohol consumption. The OBS ranges from 0 to 28, with a higher OBS indicating a more beneficial balance of pro- and anti-oxidants.

Dr. Sindhu Lakkur and her research team[1] investigated whether the OBS is associated with abnormal levels of known inflammatory biomarkers including C-reactive protein, albumin and total white blood cell count. They also assessed the association between the OBS and blood levels of lipids and lipoproteins associated with cardiovascular risk.

The scientists conducted their study with participants enrolled in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study cohort, which was originally designed to examine the causes of racial and geographic disparities in stroke rates in the US. A total of 19,825 REGARDS participants completed the mail-in questionnaire about diet and exercise and had inflammatory and lipid biomarker measurements available in the database.

Using the 14 different dietary and lifestyle factors, the researchers calculated the OBS for each participant. As there was an enormous diversity in the intake of dietary components, researchers were able to compare OBS extremes. They divided the participants into five OBS intervals (3-7 (n=861), 8-12 (n=6050), 13-17 (n=8862), 18-21 (n=3682), 21-28 (n=370)) and compared the different groups.

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Here is where the statistical magic takes place. The researchers used multivariable linear regression models to assess associations between the OBS and each biomarker and expressed the results as an adjusted odds ratio. They evaluated potential confounders by conducting covariate and sensitivity analysis.

Researchers discovered that the OBS is significantly associated with several, but not all, of the circulating inflammation markers and lipids/lipoproteins:

  • A low OBS is associated with high levels of two inflammatory markers, C-reactive protein and white blood cell counts. A low OBS is associated with low-grade inflammation, which plays a role in obesity and metabolic syndrome.
  • There is no association between the OBS and serum albumin levels (low albumin is an inflammatory marker).
  • A low OBS is associated with high LDL and high total cholesterol, but is not associated with triglycerides.
  • The association between OBS and serum HDL-cholesterol differed by sex, because on average, females had a higher HDL than males.

The study was limited by the fact that the researchers didn’t have genetic information for any of the participants or information about any infections, which would have influenced the inflammatory markers.

This study emphasizes that multiple extrinsic factors contribute to oxidative stress, and that oxidative stress can be modified by diet and other lifestyle factors. This study allowed researchers to investigate the oxidative stress-related dietary and lifestyle factors in combination, rather than as individual exposures. Other groups have also investigated the association of the OBS with various disease states and have found that it is likely disease or organ specific. We look forward to seeing if other researchers start to make significant associations between the OBS and other disease biomarkers in the future.

[1] Lakkur S, Judd S, Bostick RM, McClellan W, Flanders WD, Stevens VL, Goodman M. Oxidative stress, inflammation, and markers of cardiovascular health. Atherosclerosis. 2015 Nov;243(1):38-43. doi: 10.1016/j.atherosclerosis.2015.08.032.