John H Maher, DC, DCCN, FAAIM
www.biopharmasci.com
jmaher@biopharmasci.com
The ORAC Wars
ORAC’s Influence in the Market
Since I first began introducing to health professionals the importance of antioxidant testing of phytonutrients formulas for several years ago, “ORAC” testing has become more and more popular. Many fruit and/or vegetable functional food “greens” and “reds” products now include ORAC testing as part of their promotions to both you and your patients. Indeed, in 2003 typing in "ORAC and Antioxidants" got 3800 hits. In Feb. 2006, Google turned up 56,300! However, with competitive use of ORAC values comes misconceptions and misuse. Therefore I think it time that we review what antioxidant capacity testing means, what it doesn't mean, and where the future of such testing is going.
A Little History
Antioxidant capacity is defined as the ability of a compound to reduce pro-oxidant free radicals. In order to best combat harmful oxidation in our bodies we must supplement our internal endogenous antioxidant production (albumin and urate in plasma, glutathione, SOD, catalase in cells) with exogenous antioxidants from our diets.
The original Oxygen Radical Absorbance Capacity assay, ORAC for short, was developed at the National Institutes on Aging in Baltimore, MD.1 The NIA was thereby able to measure the antioxidant power of foods. The U.S. Agricultural Research Service considers their subsequent automation of the otherwise cumbersome ORAC assay as one of its major research accomplishments.2 In 2001, scientists at Brunswick Laboratories, Inc., Wareham, MA, developed the technology further so as to not interact with antioxidants, while demonstrating excellent photo-stability and greater economy.3 The subsequent ability to test water soluble ( hydrophillic) and lipid soluble ( lipophillic) antioxidants separately was another improvement.
The New "Comprehensive Antioxidant Profile"
The ORAC assay measures the free radical scavenging activity against the peroxyl radical, which is the most common reactive oxygen species (ROS) found in the body. But there are other important common radicals as well such as peroxynitrite, hydroxyl, singlet oxygen, and super oxideradicals. The measurement of the antioxidant capacity of a food or nutraceutical to quench a variety of free radicals is therefore desirable.
For example, in Alzheimer’s disease, Parkinson’s disease and other degenerative neurological diseases, peroxynitrite levels rise as evidenced by the accumulation of nitrotyrosine. The hydroxyl radical, extremely harmful in vivo, is a third generation species of radical derived from hydrogen peroxide, which in turn is derived from the super oxide radical.4
In actuality, there are countless combinations of internal and external antioxidants and the radicals they combat. No single measure of antioxidant status is going to provide a sufficient amount of data to evaluate in one assay the free radical scavenging activity of a food or nutraceutical. So although ORAC is the most popular and meaningful measure of antioxidant capacity currently, ORAC assays alone do not fully measure the scavenging capacity against the larger body of free radicals.
Fortunately, Brunswick Labs has also recently developed assays to determine free radical scavenging activity against other free radicals, including the peroxynitrite (NORAC) and hydroxyl radicals (yes, HORAC).5 And Columbia Phyto-Technology has developed tests for singlet oxygen.6 Already some companies are using such technologies to report a "comprehensive antioxidant profile".
Bioavailability and In Vivo Testing
To quote Jean Mayer of the USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, "...the effort to understand the health benefits of plant foods... is the characterization of their physiologically active constituents, the phytochemicals...As our knowledge grows...we will learn how best to create new products through altering their concentrations, combinations and/or their bioavailability."
In 1993 it was demonstrated that serum antioxidant activity is higher in healthy volunteers who drink red wine than those who do not.7 Therefore, quite naturally, in vivo antioxidant testing will begin to appear to demonstrate how bioavailable the supplement or functional food antioxidant activity is.
Antioxidant Testing: The Leaders and Misleaders
When I first wrote about ORAC testing in 2002, I used the research by the US government that stated that those persons who ate a high ORAC diet derived from fruits and vegetables of all the colors suffered significantly less of all the common diseases of aging. Though today there may be nutraceuticals made from one or two “super antioxidant” berries (goji), beans (coffee), fruits (mangosteen), tea (white) that have very high ORAC scores, that does not mean that they are necessarily better, stronger, or more health promoting than a wide variety of other lower ORAC plant foods.
In my article for DC in 2003, " The Physiological Functions of Phytonutrients: A Brief Introduction”, I concluded by writing:
Research shows individual phytonutrients can:
So phytonutrients are much more than just powerful antioxidants and therefore, antioxidant testing is not the “be all and end all” of phytonutrition. The take home message is that our dietary and supplementation habits would do well to include a wide variety of whole plant foods and whole food supplements nutrient dense in a broad spectrum of phytonutrients of all the colors, not just one or two super fruits or one or two colors. In this way one is much more likely to get much more benefit from the incredibly wide array of phytonutrients found in foods.
Nonetheless, ORAC and other antioxidant testing are valuable quality measures. The responsible leaders in the phytonutrient functional food field will publish and provide honest, current ORAC scores and begin to provide more comprehensive antioxidant profiles and invivo antioxidant results.
Of course, anyone who reads Consumer Reports or watches 60 Minutes knows that simply because a label or web site claims the product has “9000 ORAC units per serving” does not mean that it really does! Leading companies should provide both online and on request a copy of the original antioxidant test results for each an every batch, with the report noting from an "unopened sealed container".
Furthermore, not all these references to ORAC values are comparable to each other. How come? Some companies “promote” ORAC by the canister, bottle, or liter in order to advertise high scores like 27,000 or 80,000 to an easily fooled public. But the ORAC units are reported by labs on a per gram or a per 100 gm basis. To make it easy for consumers, results should be reported per serving. Two products could have similar ORAC per gram, but one could have twice the serving size, thus yielding twice the ORAC!
Conclusion
There is no question that ORAC has gained considerable brand recognition as a standard for antioxidant capacity, especially for suppliers and manufacturers. But the future of ORAC or any antioxidant assay will depend upon the responsible use of results when making comparisons. Otherwise the nutraceutical industry runs the risk of undermining the perceived value ORAC in the minds of consumers and health professionals alike.
At the same time, leading companies will expand their antioxidant testing to include other radicals and invivo testing, especially if the health professionals who provide these products to their patients demand them as part of their due diligence in providing the best for their patients.
John H Maher, DC, DCCN, FAAIM
www.biopahramsci.com
jmaher@biopharmasci.com
1. Cao, G.H.; Alessio, H.M.; Cutler, R.G. “Oxygen Radical Absorbency Capacity Assay for Antioxidants.” Free Radical Biol Med 1993;14(3):303-311.
2. Bank, G.; Lenoble, R. “Oxygen Radical Absorbance Capacity, Standardizing the Way We Look at Antioxidants.” Nutraceuticals World September 2002;42-45.
3. Huang, D.; Ou, B.; Hampsch-Woodill, M.; Flanagan, J.A.; Deemer, E.K. “Development and Validation of Oyxgen Radical Absorbance Capacity Assay for Lipophilic Antioxidants using Randomly Methylated Cyclodextrin as the Solubility Enhancer.” Journal of Agricultural and Food Chemistry 2002;50(7):1815-1821.
http://brunswicklabs.com/artman/uploads/jf011480w.pdf
4. http://www.nutraceuticalsworld.com/March042.htm
5. http://brunswicklabs.com/artman/uploads/jf011480w.pdf
6. The Electro Ox test tests against singlet oxygen radical using the trolox equivalent antioxidant capacity (TEAC) measure. Trolox, a water-soluble vitamin E analog, is used as the calibration standard for both the Electro Ox and the ORAC, the result expressed as micromole Trolox equivalent (TE) per gram. Of interest, ORAC does not measure carotenoid antioxidant activity as well as the Electro Ox, as singlet oxygen is well quenched by carotenoids, whereas peroxyl radicals are not so well extinguished by carotenoids.
7. Maxwell S, Cruickshank A, Thorpe G. Red wine and antioxidant activity in serum. Lancet.. 1994; 344:193-194
