Antioxidants are entering a new era of product performance.

By Ronald Prior, PhD, & Boxin Ou, PhD, David Bell, MBA, Qiuyan Zhao, MD, MBA, & HuiLin Wei, MD, PhD, Brunswick Laboratories


Antioxidants are growing up. They have emerged from their adolescence into the prime of maturity. In doing so, they have proven themselves to be versatile performers. In fact, these natural product compounds traditionally referred to as “antioxidants” may deserve a new name—”antiAGEnts.”

In the past decade, antioxidants have captured the consumer imagination—for the most part, for the better. They have become a part of the consumer vocabulary and have helped shape the landscape of nutrition products, from conventional supplements to specialty foods to cosmetics. During this time, antioxidant research has been robust. Central to the findings are: (1) that phyto-compounds traditionally called “antioxidants” demonstrate diverse characteristics; and (2) that “antioxidants” are implicated in a complex array of interconnected mechanisms in vivo.

The diversification of antioxidants’ role has important implications for natural products and the varied forms they take in the anti-aging marketplace.

The New Science of Antioxidants

There is continued interest in and questions regarding the antioxidant capacity of the diet and in vivo antioxidant status and effects on health outcomes. There is increasing evidence that the postprandial (after meal) state is an important contributing factor to chronic disease. A decrease in plasma antioxidant capacity has been observed following a meal containing macronutrients but no sources of antioxidants. The role of fruit and vegetable phenolic compounds to protect health and lower disease risk through their actions in mitigating fed-state metabolic and oxidative stressors is of interest.

Berries such as blueberries, grapes and strawberries have been shown to reduce postprandial oxidative stress. More research is needed in this area, but data from several studies summarized by Dr. Burton-Freeman suggest that consuming phenolic-rich fruits increases the antioxidant capacity of the blood. And when they are consumed with high fat and carbohydrate “pro-oxidant and pro-inflammatory” meals, they may counterbalance their negative effects. Given the content and availability of fat and carbohydrates in the Western diet, regular consumption of phenolic-rich foods, particularly in conjunction with meals, appears to be a prudent strategy to maintain oxidative balance and health.

It is becoming increasingly apparent that phenolic-rich foods may impact health outcomes through other mechanisms in addition to strictly antioxidant effects. Studies suggest that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke and consuming a diet with a high total antioxidant capacity has been related to reduced inflammation, along with increased circulating antioxidants. In a cross-sectional and randomized intervention study of 41,620 men and women, a diet rich in total antioxidant capacity was associated with a reduction in incidence of ischemic stroke and to a lesser extent in all types of stroke. In another study, positive associations were observed between dietary antioxidant capacity and adiponectin concentration and a negative relationship with inflammatory markers. As a result, an adiponectin-mediated route through which antioxidant-rich foods exert beneficial effects against inflammation and cardiovascular diseases can be hypothesized.

Consumption of a Mediterranean diet, especially rich in virgin olive oil, has also been associated with higher levels of plasma antioxidant capacity. In addition, plasma total antioxidant capacity may lead to a reduction in body weight after three years of intervention in a high cardiovascular risk population.

In another study, a group of patients with Type 2 diabetes was given a polyphenol-rich antioxidant supplement, and a decrease in LDL and an increase in HDL was observed. In addition, a byproduct of lipid peroxidation (plasma MDA) was decreased in the study group compared to the placebo group, and an increase in antioxidant defense was observed based upon increases in total plasma GSH and antioxidant capacity. These observations indicated that the polyphenol-rich antioxidant supplement may have been important in antagonizing effects on oxidative stress and lipid peroxidation in patients with Type 2 diabetes and might be beneficial in preventing cardiovascular complications.

Based on positive associations observed for total fruit and vegetable intakes and what was termed total antioxidant performance, Talegawkar et. al. suggested that it might be prudent to focus on increasing consumption of fruit, vegetables, nuts and seeds to increase total antioxidant capacity.

In this vein, accurately testing the antioxidant level in natural products and ex vivo samples remains an important task, which is why the Oxygen Radical Absorbance Capacity (ORAC) method remains relevant. And here’s why: (1) ORAC is an established standard that already plays a valuable role in the dietary supplement and functional food industries; (2) significant improvements have been made to the method; and (3) there appears to be a vital link between ORAC level and bioassay efficacy markers.

The ORAC Method Today

Briefly, ORAC was developed as an analytical tool for estimating the antioxidant capacity of substances, with an obvious application to natural products. It was an important advancement in commercially available analysis and has become a de facto standard in the natural products industry. Let’s consider some important facts:

• From the beginning, the ORAC method was considered a starting spot—not a definitive endpoint—for comprehensive antioxidant analysis.

• The original ORAC method is not a universal standard—it favors certain antioxidant substances over others (e.g., anthocyanins over carotenoids) due to the use of only one free radical source (peroxyl radical), which was chosen initially because it is the most common radical source found in the human body.

• There now exists a complementary suite of assays based on a unified ORAC chemistry that broadens the analytical scope of antioxidant testing.

This evolution process has resulted in the Total ORAC suite. It expands the ORAC platform to measure antioxidant capacity against five primary reactive oxygen species (commonly referred to as radicals)—peroxyl, hydroxyl, peroxynitrite, superoxide anion and singlet oxygen.

While Total ORAC is subject to some of the same limitations as the original ORAC method, it substantially improves broad-spectrum antioxidant analysis. It also gives evidence of the diverse antioxidant potential of natural products against radicals other than peroxyl. In some instances this potential may be specialized (e.g., carotenoids vs. singlet oxygen); in other cases, there is balanced antioxidant performance against multiple radicals. Compounds such as resveratrol and standardized ingredients such as green tea extract exhibit significant broad-spectrum antioxidant capacity.

The significance of Total ORAC is that while these primary radicals may all broadly contribute to the same outcomes—oxidative damage and corresponding disease states—they have unique characteristics that need to be addressed. Like position players on a sports team, antioxidant substances have different skill sets. And it is meaningful and valuable to know how antioxidants will perform against different opponents.