Re: Daily Highbush Blueberry Consumption for 4 Weeks, but Not 8 Weeks, Attenuates a Biomarker of Oxidative DNA Damage in Postmenopausal Women with Prehypertension or Mild Hypertension

Highbush Blueberries (Vaccinium corymbosum and V. virgatum, Ericaceae) Oxidative Stress Inflammation Antioxidant Defense Hypertension Date: 08-15-2017 HC# 021738-574 Johnson SA, Feresin RG, Navaei N, et al. Effects of daily blueberry consumption on circulating biomarkers of oxidative stress, inflammation, and antioxidant defense in postmenopausal women with pre- and stage 1-hypertension: a randomized controlled trial. Food Funct. 2017;8(1):372-380. Oxidative stress and chronic inflammation play a role in the development of hypertension, which is a risk factor for cardiovascular, cerebrovascular, and renal diseases, type 2 diabetes mellitus, and cancer. Eating vegetables and fruits, including blueberries (Vaccinium spp., Ericaceae), can help protect against oxidative stress and inflammation and the development of certain chronic diseases. In an earlier randomized, parallel-arm, double-blind, placebo-controlled clinical trial, these authors demonstrated that highbush blueberry (HB) consumption reduced systolic and diastolic blood pressure and arterial stiffness in postmenopausal women who were prehypertensive or who had stage 1 hypertension.1 In the study reported here (a secondary analysis of data collection from the previous study), the authors investigated the effects of HB, here a 50/50 blend of V. virgatum and V. corymbosum, consumption on systemic oxidative stress, inflammation, and antioxidant defense in those same women. The authors "hypothesized that daily consumption of blueberries for 8 weeks would reduce biomarkers of oxidative stress and inflammation and improve antioxidant defense compared to control." The women, aged between 45 and 65 years, were recruited through newspaper advertisements and flyers distributed in the greater Tallahassee, Florida, and surrounding areas between January 2012 and March 2013. At the first visit, the potential subjects underwent brachial blood pressure measurements and completed a medical and nutrition history. Forty-eight subjects were chosen for the 8-week trial. The subjects were randomly assigned to either the HB group (n=25) or the control group (n=23). The HB powder used in the study contained freeze-dried blueberries. The placebo powder contained maltodextrin, fructose, artificial and natural blueberry flavoring, artificial purple and red colors, citric acid, and silica dioxide. The daily intake of blueberry powder (22 g) contained 845 mg phenols and 469 mg anthocyanins. Both powders were provided by the U.S. Highbush Blueberry Council in Folsom, California. The subjects were instructed to consume one half of the daily regimen (11 g) mixed with 1 cup (240 mL) water in the morning and the second half mixed with 1 cup water at least 6 to 8 hours later. Compliance was monitored through customized calendars. At baseline and at weeks 4 and 8, the subjects underwent height and weight measurements, and body mass index was calculated. On those same visits, fasting blood draws were conducted to measure the following markers of oxidative stress, inflammation, and DNA damage: serum superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), thiobarbituric acid reactive substances (TBARS), plasma C-reactive protein (CRP), glutathione peroxidase (GPx), glutathione reductase (GR), 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). The final analysis included 20 subjects in each group. Reasons for dropping out are included in the authors' report of the earlier study.1 The authors report that after 4 weeks, plasma 8-OHdG concentrations (a marker for DNA damage) were significantly lower in the blueberry group compared with the control group (P=0.008) and compared with baseline (P=0.04). At 8 weeks, those values had increased to baseline values in the blueberry group, with no significant between-group differences seen at that time. These findings suggest that an initial protective effect could not be sustained over time. At weeks 4 and 8, the serum TNF-α levels were significantly lower compared with baseline in both groups (P<0.0001), suggesting no unique effect on TNF-α concentrations. In both groups, activities of the antioxidant enzymes GR, GPx, and SOD significantly increased at weeks 4 and 8 compared with baseline (P<0.0001), suggesting an impact of time rather than treatment. In both groups, the 8-isoprostane levels were significantly reduced after 8 weeks (P=0.003). The authors conclude that their hypothesis could not be confirmed, because the improvements seen in oxidative DNA damage at 4 weeks were not evident at 8 weeks and other biomarkers were not improved. Addressing the finding of time effects but not treatment effects, the authors say they "cannot rule out the possibility that a placebo effect, a nutritional component present in both blueberry and placebo powders, and/or lifestyle alterations such as diet, contributed to these changes," or that some parameters did not change as they were not abnormal at baseline. Among the study's limitations is the fact that only 1 dose of blueberry powder was used, which prevented the assessment of a possible dose response. Because the sample size and power were calculated based on changes in blood pressure, the study may not have been adequately powered to detect differences in other parameters. Compliance was self-reported, and changes in diet and physical activity, which may have influenced the results, were not recorded. Blood biomarkers may not reflect what occurs at the cellular and tissue levels, which may have complicated the interpretation of the findings. "This study demonstrates that daily consumption of blueberries for 4 weeks, but not 8 weeks, provided modest protection against oxidative DNA damage in a high-risk population, while all other measured parameters were not affected by blueberry consumption," conclude the authors. This study was partially supported by the U.S. Highbush Blueberry Council. —Shari Henson Reference 1Johnson SA, Figueroa A, Navaei N, et al. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial. J Acad Nutr Diet. 2015;115(3):369-377.