Oxidative stress

Effects of Tart Cherry Juice on Oxidative Stress and Inflammation

Oxidative stress, defined as an imbalance between oxidant formation and antioxidant capacity, is believed to be a key mechanism in the aging process and a variety of age-related chronic diseases.

In recent years, oxidative stress in vivo has most commonly been measured by determining the levels of plasma F₂-isoprostanes. A recent comparative study has validated isoprostane measurement as the most sensitive and reproducible indicator of a variety of techniques for estimating oxidative stress in an experimental model.

Plasma and/or urine F₂-isoprostanes levels are increased in humans during chronic conditions such as obesity hypercholesterolemia, diabetes, and smoking. In contrast, F₂-isoprostane levels do not appear to increase with age in humans, although significant increases have been shown in very aged rats. These finding suggest that there may be a diminution in the capacity to resist oxidative stress that is not apparent under normal conditions, but could become apparent when challenged by additional oxidant stresses.

Such a challenge can be accomplished by producing acute transient oxidative stress in a limited area by inducing a regional ischemia/reperfusion and measuring the systemic resistance to such stress. Ischemia/reperfusion is a well-established oxidative stress with the extent of the oxidation being determined by the duration and extent of the ischemic event. We use a timed inflation of a blood pressure cuff above arterial pressure on a subject's arm followed by deflation, a protocol that significantly increases free F₂-isoprostanes.

This method appears to integrate contributions of multiple resistance mechanisms to oxidative stress, including small molecular antioxidants, antioxidant enzymes, down-regulation of oxidant generating signaling enzymes, and modulators of leukocyte activation. Data from our laboratory, using the I-R trial, shows that older individuals have a significantly greater F₂-isoprostane response as compared to young individuals.

These results suggest that while there were no age-related differences in baseline values, the capacity to counteract the oxidative challenge was diminished with age. This study follows the previous study and is designed to answer the question whether the capacity to resist oxidative stress can be increased through interventions designed to increase the antioxidant capacity.

The primary aim of the proposed study is to evaluate the effects of a dietary source of antioxidants on the capacity to resist oxidative stress as measured by the response elicited by the forearm I-R trial.

An important source of antioxidants in the diet comes from a class of secondary plant metabolites known as flavonoids. A specific type of flavonoid found in plants, called anthocyanin, has been shown to be a powerful antioxidant that helps protect the plant from radicals formed by UV light and during metabolic processes.

This antioxidant property is conserved even after consumption by another organism. Flavonoids and other phenolic compounds have powerful antioxidant activities in vitro and in vivo, being able to scavenge diverse ROS species or inhibit their formation.

Tart cherries have been identified to have antioxidant cyaniding glycosides and cyclooxygenase inhibitory flavonoids, which makes them a good source of phenolic compounds with antioxidant and anti-inflammatory properties. Consumption of about 45 Bing sweet cherries a day has been shown to reduce circulating concentrations of inflammatory markers in healthy men and women.

A recent study in young individuals found that a 4-week intervention with an anthocyanin/polyphenolic-rich fruit juice resulted in reduced oxidative DNA damage, increased glutathione levels, but no differences in markers of lipid peroxidation. However, their outcome variables were only measured under non-stimulated conditions which may explain some of the non-significant findings.

In summary, we know that aging is associated with a progressive decline in the ability of the organism to resist oxidative stress and repair damage, and reduced capacity to resist oxidative stress is associated with increased morbidity and mortality. It is possible that interventions aimed at lowering oxidative stress may only show results in individuals that already have increased oxidative stress and/or reduced capacity to resist oxidative stress. For example, supplementation with high levels of vitamin E does not lower resting F₂-isoprostane levels in healthy adults, but does lower elevated F₂-isoprostane levels in individuals with hypercholesterolemia.

The lack of an effect of such dietary antioxidants in healthy adults had led some to hypothesize that they are of no benefit in increasing functional life span in apparently normal individuals. However, if older adults supplemented with dietary antioxidants such as a tart cherry juice blend, showed significant decreases in the levels of F₂-isoprostanes formed after local ischemia-reperfusion stress in comparison to placebo, it would suggest that such supplementation may in fact have significant impact on resistance to oxidation and might therefore affect morbidity.

KLRI will recruit 12 healthy, non-smoking adult men and women, between the ages of 55 and 80 years.

The exclusion criteria include:

• Use of anti-oxidant supplements, in excess of standard multi-vitamins (1 tablet/day)
• Current hormone replacement therapy
• Any history of significant chronic disease
• Uncontrolled hypertension: (systolic BP>140 or diastolic BP>85 mmHg on at least 2 measurement, at least 10 minutes apart)
• Body mass index (BMI) > 30 kg/m2
• Use of anti-inflammatory medication
• High physical activity level