Lisa Olivo, Associate Editor03.02.15
Antioxidants assist in managing and preventing a wide range of health conditions. These essential nutrients combat oxidative stress, support immunity, promote heart health, and can protect the eyes, brain, joints and skin. In addition, strong consumer awareness for antioxidants—bolstered by sound clinical research—makes this market a powerful player in the nutraceuticals space.
A handful of ingredients saw solid growth this past year, according to SPINS data across natural and conventional departments for the 52 weeks ending Dec. 28, 2014. Supplements with turmeric earned approximately $426,000 (up 114%) from 2013; vitamin A reached $14.8 million (up 100%); and vitamin C (not including Ester-C) took in about $331 million (up 4.6%).
However, a saturated market seems to have diluted some of the category’s potency. Despite a strong overall showing, sales of several antioxidant supplements slumped in 2014. SPINS reported that sales of green teas and green tea supplements declined 16% to about $60 million; resveratrol fell to $5.4 million, down 18.3%; CoQ10 earned approximately $151 million, down 2.3%; beta-carotene (non-combo) fell 26.2% to about $711,000; vitamin E (not Ester-E) was down 0.6% to around $39.3 million; selenium fell by 0.2% earning about $2 million; and lutein stayed flat at around $31 million.
Hartley Pond, vice president of technical sales, FutureCeuticals, Inc., Momence, IL, suggested the prevalence of antioxidant claims has lessened consumer appeal. “The term itself is becoming generalized to a point that all many consumers hear is white noise.”
However, he said, “The conversation has turned to free-radical scavenging and demonstrated reactive oxygen species (ROS) scavenging evidence in the body via clinical research.”
How can companies differentiate their products from the pack? Targeted, science-backed, condition-specific approaches could help cut through the noise, and reintroduce consumers to the important role antioxidants play for their health.
“The trend seems to have moved from general antioxidants to ones that have shown real promise for certain applications,” noted James Liu, general manager of SeabuckWonders Inc., Chicago, IL. “The more human studies available, the better.”
Market Drivers
Antioxidants target a wide range of health concerns today, which is perhaps why 60% of consumers stay loyal to a product due to antioxidant content, according to market research firm Packaged Facts, Rockville MD.
A 2012 Gallup Study of Nutrient Knowledge & Consumption found that 47% of consumers link antioxidants to immunity; 44% to heart health; 35% to removing free radicals; 28% to improved memory; 27% to eye health; 26% to joint health; 26% to clearer skin; and 21% to fewer wrinkles.
In addition to these indication areas, several new themes and health concerns are helping to advance the sector.
Natural
Some experts see the popularity of antioxidants tied to consumer desire for foods and beverages that are naturally healthy. Mintel identified strong consumer demand for transparency, with 80% of U.S. consumers looking for nutritional claims when buying food, and 38% wanting all-natural products.
How users want to consume these naturally beneficial ingredients is changing as well. While in previous years supplements may have been the go-to source, consumers today are looking for foods naturally rich in antioxidants, according to Dr. A. Elizabeth Sloan and Catherine Adams Hutt, Sloan Trends, Inc., Escondido, CA. A 2013 Gallup Study of Nutrient Knowledge and Consumption reported that 28% of consumers make a strong effort to eat more foods naturally “rich-in” antioxidants. In 2006, 79% of antioxidant users were getting them from a supplement, but in 2013 just 49% took antioxidants in supplement form. Conversely, there has been steady growth for naturally antioxidant-rich foods (up 76% in 2013 from 57% in 2006), and naturally antioxidant-rich beverages (up 44% in 2013 from 34% in 2006). Fortified foods and beverages have stayed somewhat flat.
Mr. Liu of SeabuckWonders said antioxidants that occur naturally in herbs and spices are gaining popularity. “Many of these natural antioxidants (including plant extracts) have been incorporated into food products and supplements. The general public is becoming more educated on what antioxidants are and how they can benefit our health. Not only are antioxidants showing up more in food and health supplements, they have made their way into the cosmeceutical world.”
On the other hand, Jeff Wuagneux, president and CEO of RFI Ingredients, Blauvelt, NY, believes the tides are shifting away from extracts, and instead an emphasis on natural “whole food” ingredients is emerging. He pointed to RFI’s FermaPro Black Garlic, which is a whole food, non-extracted fermented garlic, as a natural antioxidant on the rise. “While it’s standardized to a marker compound (in this case S-Acetyl Cysteine (SAC)), a more stable and potent antioxidant than allicin to guarantee potency and quality, it is not a purified extract and relies on fermentation to increase its level of SAC rather than extraction.”
Significant interest in natural and fruit-based antioxidants has emerged, according to Rick Kaiser, vice president of sales and marketing, Natreon Inc., New Brunswick, NJ, which is currently conducting clinical research on its “new and novel fruit-based antioxidants that appeal to today’s consumers because of their functionality and efficacy.” The company’s research is investigating Capros Indian Gooseberry, and AyuFlex, a water-soluble product derived from Terminalia chebula fruit, for their benefits related to cardiovascular health. “There are now eight human studies demonstrating the cardiovascular benefits of Capros and five studies on AyuFlex for multiple consumer applications, like joint health and cardiovascular health,” Mr. Kaiser said.
Effective, natural products will attract antioxidant users, according to Efrat Kat, director of marketing and sales at Algatechnologies Ltd., Kibbutz Ketura, Israel, which supplies AstaPure natural astaxanthin. “Consumers prefer antioxidants with proven health benefits that are naturally sourced, as opposed to artificial/synthetic products that can be unsafe or ineffective in the long-term.”
Golan Raz, senior vice president of commercialization at LycoRed, Orange, NJ, believes this shift toward natural products is disrupting the traditional antioxidant market. “As we see a transition from the basic vitamins and minerals to whole food-based supplements, the fame of these basic ones is declining. The main reason is a growing innovation around whole food-based products, natural carotenoids and polyphenols, as well as the fact that most vitamins sold are synthetic.”
Preventive Health
Roughly 10,000 Baby Boomers turn 65 each day, and will continue to do so for the next 19 years, according to the Pew Research Center. As this large generation enters the “golden years,” many are utilizing dietary supplements, especially antioxidants, to preserve their heath.
“Our aging populations are increasingly aware of health risks and related preventable measures due to various public education campaigns, recommendations from physicians and nutritionists, and periodic scientific news,” noted Catherine David, product manager, Neptune Technologies & Bioressources Inc., Laval, Quebec, Canada. “There is a definite trend toward more proactive, preventive behavior on the part of consumers than previous reactive modifications in lifestyle changes following tardy diagnosis or treatment.”
Eric Ciappio, scientific leader of nutrition science and advocacy, DSM Nutritional Products, Parsippany, NJ, said antioxidant trends are highly correlated with the general consumer shift toward preventive health. Antioxidants are appealing due to their ability to reduce cell-damaging free radicals. “Antioxidants are said to have a whole array of health benefits,” said Mr. Ciappio, “most of which are believed to be long-term and cumulative, rather than promising a quick fix for an existing condition.” Anti-aging and the prevention of the eye disease macular degeneration, cancer and stroke are good examples of conditions that could benefit from antioxidant use long-term, he added.
Oxidative Stress
Antioxidants are essential to protecting the body from oxidative stress from free radicals, which Mr. Ciappio said, “are a byproduct of normal metabolism as well as certain environmental factors (e.g., cigarette smoke).”
An unbalanced diet, extreme exercising, modern lifestyle and air pollution can also contribute to oxidative stress for people in all stages of life, according to Algatechnologies’ Ms. Kat. “The DNA in every cell in the human body suffers about 10,000 ‘hits’ from free radicals each day. It is therefore very important for everyone to uphold a diet rich in antioxidants and to consume supplements with special antioxidants that are no longer readily available in our diet, such as natural astaxanthin.”
Combating exercise-induced oxidative stress is also an emerging trend. “Exercise produces a lot of free radicals in the mitochondria as a byproduct of converting glucose to energy,” explained Brien Quirk, director of R&D for the San Jose, CA-based Draco Natural Products. “Muscle damage from exercise causes inflammation, which results in free radical production. Antioxidants have been shown to improve muscle recovery time and lessen pain and inflammation following exercise.”
In addition, antioxidants support consumers looking to protect their skin from the harmful effects of free radicals, which he said “are known to damage the lipid membrane of skin cells, and contribute to wrinkles and the uneven pigmentation of skin.” Free radical production from UV and excessive light exposure to the retina can lead to macular degeneration of the eyes, he added.
Despite the many benefits of these free-radical scavenging nutrients, a recent New York Times blog post “Are Vitamin Drinks a Bad Idea?” suggested there can be too much of a good thing. According to the report, many functional beverages are offering vitamins and nutrients at levels well past the limits of safety established by the Institute of Medicine. In the case of antioxidant drinks—which are wildly popular and plentiful—an excess of antioxidants could be neutralizing too many free radicals. This may be problematic, as they are needed for some beneficial processes in the body, such as fighting off infection and cancer cells.
Cardiovascular Health
The World Health Organization reported that cardiovascular disease (CVD) is the leading cause of death globally, resulting in 17.5 million deaths in 2012. Antioxidants may benefit many health factors that lead to CVD, including blood pressure, cholesterol and circulation.
Interest in the benefits of antioxidants for heart health and blood pressure are strong drivers for this market, noted Neptune’s Ms. David. Antioxidant use for cardiovascular health, plus consumers’ interest in foods naturally rich in antioxidants, has contributed to the antioxidant market’s overall growth, she said.
“It is known that oxidized LDL cholesterol is more atherogenic (artery clogging) than when it is non-oxidized,” said Draco’s Mr. Quirk, noting antioxidant’s benefits for healthy cholesterol management.
Antioxidants from blueberries could emerge as an important ingredient for cardiovascular health, he added. “One phyto-compound with antioxidant effects that is growing in its market share is a phenolic known as pterostilbene, which is found in blueberries and has some benefits similar to resveratrol for cardiovascular health.”
Shaheen Majeed, marketing director, Sabinsa, East Windsor, NJ, suggested antioxidant products addressing healthy circulation and the reversal or prevention of atherosclerosis could help expand the antioxidant market, particularly in the U.S., Europe and China.
“Atherosclerosis was the number one health issue consumers tried to address with condition-specific dietary supplements in 2011, followed by lowering cholesterol and blood pressure. One-third (34%) of women and half (52%) of men have been diagnosed with significant plaque building up in their arteries thanks to improved imaging techniques that are now more commonly employed in diagnostic testing.” Additionally, Mr. Majeed said, “Circulation is now a bigger mass market opportunity than LDL or HDL cholesterol in 2012, according to Sloan Trends’ TrendSense.”
Inflammation
Arthritis and diabetes, two significant concerns for the aging population, involve inflammatory processes that generate extra free radicals, according to Mr. Quirk. Antioxidants, he said, have been shown to improve joint health by reducing inflammation caused by free radicals, and may also help to reduce blood sugar among diabetics.
Savvy Consumers
With health benefits linked to a wide array of conditions, consumers rely on antioxidant ingredients at all walks of life.
In 2013, HealthFocus International conducted a study that indicated a steady percentage of shoppers consistently want to see label information on antioxidants, with a spike in interest in 2008. Likewise, increased usage is more or less stable, with the exception of a surge in 2010. The study also revealed 40% of shoppers surveyed said that a “Good source of antioxidants is extremely/very important on labels,” and 20% said they “increased use of antioxidants over the past two years.”
Shoppers older than 50 felt most strongly about the importance of antioxidants on the label (45% in their 50s and early 60s and 44% 65-plus); the study also showed an increase in antioxidant usage was highest among men (24%) and highest earners (24%) and lowest among the oldest shoppers (14%).
As a result of numerous age-related health issues, older consumers are a clear and powerful consumer base. “The aging population, consisting of Baby Boomers with disposable income, is still the main buyer of antioxidants,” commented Mr. Wuagneux of RFI.
Pete Maletto, president and senior scientist, PTM Food Consulting, Point Pleasant, NJ, said this mature and educated audience is looking to prolong good health with a variety of new products targeting multiple health concerns. “New-age food-based antioxidants possess amazing anti-inflammatory benefits that far outreach the basic free radical scavenging vitamins of the 1980s and 1990s.”
Mr. Majeed said interest in cognitive health among aging consumers is a key market driver. “In the top 10 most important health issues, three involve brain health/mental acuity, memory and mental agility. Twenty-seven percent of consumers purchased antioxidant-containing foods that they believe will affect mental acuity and memory in 2010. Lack of mental acuity is in the top three U.S. health concerns. This may be due to the fact that 80% of consumers surveyed had one or more relatives who suffered from Alzheimer’s, Parkinson’s or senility. Antioxidant supplements should be formulated to take advantage of this trend.”
In general though, the overall consumer shift toward healthier, less processed and nutritious foods are leading more consumers to antioxidants. Mr. Liu of SeabuckWonders said, “More people want to adopt healthier habits and are more aware of natural remedies for battling disease. This awareness is due in part to availability of nutritional information growing and more coverage by experts in popular media (Dr. Oz for example).” He pointed to the growth of the alternative diet market, including groups like vegans and paleo-diet followers, bringing a whole new crop of consumers to push the antioxidant market forward.
Emerging Antioxidants
The strong body of science validating beta-carotene, vitamin C and vitamin E has led the U.S. Food and Drug Administration (FDA) to qualify these three ingredients as the only antioxidants to be used in labeling and nutrient content claims, noted Rachel Murphy, scientific leader, nutrition science and advocacy, DSM. Therefore, these three vitamins are primarily used in fortification of foods and beverages, such as fruit juices and cereals, she said. Fortification is an important way to fill the nutritional gaps for consumers deficient in antioxidants. “From a nutrient perspective, there are large gaps in dietary intake of antioxidant vitamins; over 93% of adults in America do not meet the estimated average requirements for vitamin E, and over 50% do not meet recommended intakes for vitamin A and C.”
DSM’s Mr. Ciappio commented that these more established and popular antioxidants, particularly vitamins C and E, are often “underappreciated despite the tremendous and still growing body of literature supporting their role in human health.”
For example, he pointed to the results of a major clinical trial published in the Journal of the American Medical Association (JAMA) in 2014, which demonstrated the role of vitamin E in slowing the progression of Alzheimer’s disease. He added, “Data from national surveys show that people do not get enough vitamin E or vitamin C in their diets, so for many it makes sense to consider using a dietary supplement or fortified food that contains these antioxidants to help meet their nutritional needs.”
While food fortification can help to improve consumer nutrition, there are many common foods naturally rich in antioxidants that are backed by sound clinical research. For example, Mr. Ciappio pointed to olive oil, which is a staple in the Mediterranean diet and has been linked to heart health for more than 60 years. However, he said, “it was only recently established that antioxidant polyphenols found within olive oil, such as hydroxytyrosol, can protect blood lipids from oxidative damage and help maintain heart health. This science was so compelling that the European Food Safety Authority (EFSA) authorized a health claim for hydroxytyrosol in 2011.”
In addition, he said spinach and eggs contain antioxidant carotenoids lutein and zeaxanthin, which have been shown to support eye health by absorbing damaging blue light that enters the eye. He also cited research published in Nutrition Review (2014) that demonstrated a link between these nutrients and brain health.
Mr. Pond of FutureCeuticals said his company is researching numerous fruits and vegetables with a range of ORAC scores (oxygen radical absorbance capacity), and observing in vivo changes of various free radicals in the blood. “Our research indicates substantial antioxidant benefits for certain natural products when used at optimal dosages. Dose response and bioavailability are critical keys to having a proper understanding of any antioxidant value and, more importantly, any activity of a product in vivo.”
In its research on the free radical scavenging activity of fruits, vegetables and grains, Mr. Pond said FutureCeuticals is “regularly seeing a bell curve effect whereby, above a certain level, antioxidant materials actually become pro-oxidative.” Proper antioxidant science often involves careful consideration of the correct dose for a given category of phenolic compounds. “We are using short-term (acute) dose response studies in order to substantiate bioavailability either directly by quantitative analytical procedures, or indirectly by function, as observed under properly controlled conditions in the acute setting, as is appropriate for natural products.”
Late in 2014, FutureCeuticals published a human clinical study that showed effects of its Spectra natural supplement on changes in oxidative and nitrosative stress markers in vivo. The study determined that a 100 mg dose actually yielded the best in vivo effect. “Interestingly, the results also indicated a spike in nitric oxide and increased oxygen utilization after ingestion of Spectra,” noted Mr. Pond.
Mr. Raz, of LycoRed, predicted targeted combinations of antioxidants could be the next trend in the market. “While in the past, single-sourced antioxidants were broadly used (vitamin C, vitamin E, beta-carotene and others), advanced scientific research indicates specific compositions that combine several antioxidants at an optimized dosage may drive a much more powerful effect.”
As a result of this ongoing area of research, more product introductions based on combinations of whole fruits and vegetable extracts have emerged. “Combinations made of tomatoes, berries, cocoa, algae, grapes and other whole foods are being studied and commercialized for indicating specific targets, including cardiovascular health, vision health, prostate health, anti-aging, sports recovery and many more.”
An emerging star in recent years, turmeric is garnering significant attention. PTM’s Mr. Maletto said turmeric/curcumin is an excellent antioxidant linked to life extension.
Nutrition Business Journal projected turmeric/curcumin would be among the top 10 best-selling supplements through 2016, virtually doubling in sales from $103 million in 2013 to $235 million, with a CAGR of 21.5%.
Mr. Maletto attributed growth to extensive research backing the inhibition of cancer, arthritis, diabetes, cardiovascular disease, osteoporosis, and potentially reversing the pathological processes underlying Alzheimer’s disease. For example, curcumin may reduce deadly beta amyloid plaques in the brain. It may also assist the liver in processing viruses such as hepatitis, and other conditions.
Additionally, he said one of curcumin’s most important mechanisms of action is “its ability to inhibit activation of the transcription factor, nuclear factor-kappa B (NF-kB), a potent inducer of chronic inflammation. NF-kB is a protein that acts as a sort of switch, turning inflammation on by activating genes involved in the production of inflammatory compounds. As NF-kB activation has been implicated in all the stages of carcinogenesis, this transcription factor is a potential target in cancer prevention and is the subject of intensive research.”
Switzerland-based Frutarom BU Health’s technical specialist, Eden Beth, said antioxidants derived from caffeine-containing botanicals such as green tea, yerba mate and coffee are known to be naturally rich in beneficial compounds. These antioxidant-rich ingredients are being utilized in “dietary supplements and increasingly in functional foods and functional beverages—ranging from sophisticated instant beverages to RTD (ready-to-drink), single shots and premium, niche bottled coffees.”
“Yerba mate and other South American herbs used for teas and in beverages often will have high levels of naturally-occurring antioxidants in the form of flavonoids—or more generally characterized as polyphenols. As one example, Yerba mate (Ilex paraguariensis) such as Frutarom’s Finomate is tested for different compounds and is a naturally antioxidant-rich plant.”
Alpha-lipoic acid (ALA) and astaxanthin are two unique antioxidants that have recently emerged in the supplement market, according to Neptune’s Ms. David. “ALA is usually sold under its own name, whereas astaxanthin can be found either as a standalone product or within marine sources like omega-3 krill oil.”
What makes ALA unique, she said, is that it functions in water and fat (unlike some more common antioxidants) and it appears to be able to recycle other antioxidants after they have been used up. As for astaxanthin, Ms. David explained, “it is one of the most powerful antioxidants; it is bioavailable throughout the body and is quite potent when compared to other antioxidants. Astaxanthin has been shown to reduce oxidative stress, which is believed to be the main cause of cellular aging.”
The astaxanthin found within krill oil also helps “stabilize liposomes in the body that protect important fatty acids from degradation by harsh stomach acids, which in turn allows more of them to be absorbed by the body. This powerful antioxidant provides exceptional protection against oxidation, greatly extending the life of the product,” she said.
AstaReal, Inc., Burlington, NJ, offers AstaREAL natural astaxanthin. Technical support with the company, Janice Brown, said consumers are becoming more aware of astaxanthin as an alternative to traditional antioxidant sources.
Discussing the potency of AstaReal, she cited research published in Carotenoid Science in 2007. “Studies show AstaREAL natural astaxanthin to be 6,000 times stronger than vitamin C at ROS (reactive oxygen species) quenching. The same study indicated AstaREAL natural astaxanthin to also be 800 times stronger than CoQ10 and 40 times stronger than beta-carotene.”
Ms. Kat of Algatech noted that the growth of astaxanthin has much to do with the depth of research validating the overall carotenoid category. “Carotenoids are very powerful antioxidants; they absorb light due to their special bonding structure, and hence provide defense from excessive light radiation and photo-oxidative damage,” she explained.
AstaPure astaxanthin has also been shown in multiple studies to assist in protecting the body under stress conditions, she said. It is widely used in formulations related to brain function, sports activity, skin health and more.
Mr. Kaiser of Natreon said that PrimaVie shilajit is an important emerging ingredient for the company. “With an ORAC rating as high as many superfruits, PrimaVie is an ancient Ayurvedic ingredient used for thousands of years. Using modern clinical and animal research, Natreon has shown PrimaVie functions as a mitochondrial antioxidant, restoring ATP and boosting energy.”
The superfruit craze still holds weight in the antioxidant market, according to Mr. Liu of SeabuckWonders, who said these ingredients have dominated the category for the last five years, with new introductions to the group each year. “Some big ones to look out for are amla and sea buckthorn,” he said, as well as pterostilbene.
Flavonoids have the capability of chelating certain trace elements such as copper and ferrous iron so that they won’t generate toxic hydroxyl radicals, according to Draco’s Mr. Quirk, “Many of the flavonoids found in green tea, blueberries and other anthocyanin rich foods have this effect and help to protect cell membranes and cholesterol from being oxidized.” Fruits and vegetables contain an abundance of flavonoids that reduce LDL oxidation, free radicals generated by inflammation, and free radicals from reactions with copper and iron ions, he added.
Mr. Majeed of Sabinsa said that pomegranate juice and blueberries are the fastest growing antioxidant-containing fruits and fruit products. “Mangosteen, goji berry and acai had the highest superfruit sales in 2012. Passion fruit, guava, paw paw and dragon fruit were the best-selling superfruits in 2011,” he said.
He also noted that cocoa and other chocolate-containing products are generating consumer awareness on par with antioxidants and vitamins. “Polyphenols and flavonoids remain the strongest phytochemical mass market ingredients,” he said. “Spices, chick peas, lentils, seeds and nuts are among the hottest new super foods containing antioxidants.”
Changing Tides
Despite the many antioxidants gaining consumer attention, some of the traditional offerings in this space have seen a decline for a variety of reasons.
Beta-carotene, for example, has lost some favor with consumers, according to Draco’s Mr. Quirk, as a clinical study reported smokers taking extra beta-carotene had an increased risk of lung cancer. He also cited studies demonstrating that “selenium supplementation may increase the risk of diabetes,” as a deterrent for the use of this ingredient. “Vitamin E has come under scrutiny in some studies that have shown increased rate of death from all causes at supplementation of 400 IU of alpha tocopherol,” Mr. Draco said. “Some have theorized that taking only extra alpha tocopherol causes a deficiency of the form of vitamin E known as gamma tocopherol, which is vital for quenching specific free radicals (i.e., peroxynitrate radicals).”
Mr. Pond of FutureCeuticals pointed to a dip in superfruit interest, suggesting better science was needed in some cases. “Antioxidants, including some superfruits, that simply have high ORAC levels, but lack extensive human clinical studies, have lost some of their initial appeal to consumers.”
Natreon’s Mr. Kaiser said mature antioxidants like vitamins E and C, and antioxidant minerals have plateaued. “There is a great deal of media skepticism as to the long-term health benefits, and the VMS [vitamins, minerals, supplements] industry hasn’t been effective at refuting the negative press.”
“The worst hit in recent years has been isolated vitamin E supplements,” noted Mr. Liu of SeabuckWonders. “One study, which followed subjects regularly taking vitamin E showed that there were no benefits over a course of nine years. Though some say this study was flawed, the study was publicized and consumers listened.” He cautioned that consumers are taking notice when an ingredient gets bad press.
DSM’s Mr. Ciappio said the antioxidant meso-zeaxanthin has also come under some scrutiny. Meso-zeaxanthin, he said “is a metabolic byproduct of the important antioxidant lutein that accumulates in the eye. It is not naturally found in the food supply in appreciable amounts, but can be present in certain lutein/zeaxanthin dietary supplements (often labeled in the ingredient line as ‘zeaxanthin isomers’).” In 2014, the use of supplemental meso-zeaxanthin was linked to a skin condition known as toxidermia in France, Mr. Ciappio said. In light of these findings, he cautioned against using supplements containing this substance until more research and testing is done to prove its safety.
Sound Science
There are a variety of scientifically validated testing methods to ensure the efficacy and potency of antioxidant supplements—the most common being ORAC value, noted Mr. Maletto of PTM. This test, he said “attempts to quantify the ‘total antioxidant capacity’ (TAC) of a food by placing a sample of the food in a test tube, along with certain molecules that generate free radical activity and certain other molecules that are vulnerable to oxidation. After a while, they measure how well the sample protected the vulnerable molecules from oxidation by the free radicals. The less free radical damage there is, the higher the antioxidant capacity of the test substance.”
Mr. Pond said FutureCeuticals has a unique perspective on testing methodology for antioxidants, “as we have been intimately involved with the development and evolution of ORAC, ORAC-FN, and now the next logical step: detecting antioxidant activity real-time within the human body. Dr. Boris Nemzer, FutureCeuticals director of R&D and quality assurance, worked closely with Dr. Boxin Ou and Brunswick Labs at the very beginning of the ORAC development, and also with subsequent improvements and expansions to antioxidant potential testing.”
Ensuring these antioxidants reach the bloodstream is another matter that must be examined, according to RFI’s Mr. Wuagneux. He said ORAC testing can be done on blood, which RFI did with its OxyPHyte Ultra Blend more than 10 years ago.
“A newer, more relevant form of antioxidant testing is plasma antioxidant capacity whereby a test substance is administered in vivo to a human volunteer to see how well it increases the antioxidant capacity in the blood and takes into account the absorption of a test substance,” noted Mr. Quirk. “Since only 5% of some flavonoids such as EGCG (Epigallocatechin gallate) and quercetin are known to be absorbed, it does not make sense to test these substances in a traditional test tube assay (in vitro) as with the older ORAC method, because it would not be an accurate indication of how well utilized the antioxidant source is.”
Algatech’s Ms. Kat pointed to antioxidant testing methods that “have been approved by pharmacopeias around the world such as ET-based (electron transfer) or HAT-Based (hydrogen atom transfer), represented by the ORAC assay.” This evolving technology, she said, has advanced antioxidant methods for more accurate results, but also discredited ineffective compounds. For example, she explained “it’s possible to determine the purity of astaxanthin by using HPLC (high-performance liquid chromatography).”
In addition to ORAC, Mr. Liu explained many other assays have been developed, such as ORAX or PAOXI, which measure antioxidants in different ways. “Nowadays, many researchers think that it is much wiser to combine ORAC’s different versions (there are three) with other assays to get a more complete understanding. They refer to this as RACI or relative antioxidant capacity index.” An additional assay is the CAA, which was introduced around 2007. This method, Mr. Liu said, included a clearer picture of antioxidant metabolism than was previously available. Lastly, he explained that CAP-e is an assay that is especially important because it can measure the bioavailability of antioxidants. He noted, however, “Many of the assays have come under scrutiny, including ORAC. The methods used, and our understanding of how antioxidants work, are constantly evolving.”
A handful of ingredients saw solid growth this past year, according to SPINS data across natural and conventional departments for the 52 weeks ending Dec. 28, 2014. Supplements with turmeric earned approximately $426,000 (up 114%) from 2013; vitamin A reached $14.8 million (up 100%); and vitamin C (not including Ester-C) took in about $331 million (up 4.6%).
However, a saturated market seems to have diluted some of the category’s potency. Despite a strong overall showing, sales of several antioxidant supplements slumped in 2014. SPINS reported that sales of green teas and green tea supplements declined 16% to about $60 million; resveratrol fell to $5.4 million, down 18.3%; CoQ10 earned approximately $151 million, down 2.3%; beta-carotene (non-combo) fell 26.2% to about $711,000; vitamin E (not Ester-E) was down 0.6% to around $39.3 million; selenium fell by 0.2% earning about $2 million; and lutein stayed flat at around $31 million.
Hartley Pond, vice president of technical sales, FutureCeuticals, Inc., Momence, IL, suggested the prevalence of antioxidant claims has lessened consumer appeal. “The term itself is becoming generalized to a point that all many consumers hear is white noise.”
However, he said, “The conversation has turned to free-radical scavenging and demonstrated reactive oxygen species (ROS) scavenging evidence in the body via clinical research.”
How can companies differentiate their products from the pack? Targeted, science-backed, condition-specific approaches could help cut through the noise, and reintroduce consumers to the important role antioxidants play for their health.
“The trend seems to have moved from general antioxidants to ones that have shown real promise for certain applications,” noted James Liu, general manager of SeabuckWonders Inc., Chicago, IL. “The more human studies available, the better.”
Market Drivers
Antioxidants target a wide range of health concerns today, which is perhaps why 60% of consumers stay loyal to a product due to antioxidant content, according to market research firm Packaged Facts, Rockville MD.
A 2012 Gallup Study of Nutrient Knowledge & Consumption found that 47% of consumers link antioxidants to immunity; 44% to heart health; 35% to removing free radicals; 28% to improved memory; 27% to eye health; 26% to joint health; 26% to clearer skin; and 21% to fewer wrinkles.
In addition to these indication areas, several new themes and health concerns are helping to advance the sector.
Natural
Some experts see the popularity of antioxidants tied to consumer desire for foods and beverages that are naturally healthy. Mintel identified strong consumer demand for transparency, with 80% of U.S. consumers looking for nutritional claims when buying food, and 38% wanting all-natural products.
How users want to consume these naturally beneficial ingredients is changing as well. While in previous years supplements may have been the go-to source, consumers today are looking for foods naturally rich in antioxidants, according to Dr. A. Elizabeth Sloan and Catherine Adams Hutt, Sloan Trends, Inc., Escondido, CA. A 2013 Gallup Study of Nutrient Knowledge and Consumption reported that 28% of consumers make a strong effort to eat more foods naturally “rich-in” antioxidants. In 2006, 79% of antioxidant users were getting them from a supplement, but in 2013 just 49% took antioxidants in supplement form. Conversely, there has been steady growth for naturally antioxidant-rich foods (up 76% in 2013 from 57% in 2006), and naturally antioxidant-rich beverages (up 44% in 2013 from 34% in 2006). Fortified foods and beverages have stayed somewhat flat.
Mr. Liu of SeabuckWonders said antioxidants that occur naturally in herbs and spices are gaining popularity. “Many of these natural antioxidants (including plant extracts) have been incorporated into food products and supplements. The general public is becoming more educated on what antioxidants are and how they can benefit our health. Not only are antioxidants showing up more in food and health supplements, they have made their way into the cosmeceutical world.”
On the other hand, Jeff Wuagneux, president and CEO of RFI Ingredients, Blauvelt, NY, believes the tides are shifting away from extracts, and instead an emphasis on natural “whole food” ingredients is emerging. He pointed to RFI’s FermaPro Black Garlic, which is a whole food, non-extracted fermented garlic, as a natural antioxidant on the rise. “While it’s standardized to a marker compound (in this case S-Acetyl Cysteine (SAC)), a more stable and potent antioxidant than allicin to guarantee potency and quality, it is not a purified extract and relies on fermentation to increase its level of SAC rather than extraction.”
Significant interest in natural and fruit-based antioxidants has emerged, according to Rick Kaiser, vice president of sales and marketing, Natreon Inc., New Brunswick, NJ, which is currently conducting clinical research on its “new and novel fruit-based antioxidants that appeal to today’s consumers because of their functionality and efficacy.” The company’s research is investigating Capros Indian Gooseberry, and AyuFlex, a water-soluble product derived from Terminalia chebula fruit, for their benefits related to cardiovascular health. “There are now eight human studies demonstrating the cardiovascular benefits of Capros and five studies on AyuFlex for multiple consumer applications, like joint health and cardiovascular health,” Mr. Kaiser said.
Effective, natural products will attract antioxidant users, according to Efrat Kat, director of marketing and sales at Algatechnologies Ltd., Kibbutz Ketura, Israel, which supplies AstaPure natural astaxanthin. “Consumers prefer antioxidants with proven health benefits that are naturally sourced, as opposed to artificial/synthetic products that can be unsafe or ineffective in the long-term.”
Golan Raz, senior vice president of commercialization at LycoRed, Orange, NJ, believes this shift toward natural products is disrupting the traditional antioxidant market. “As we see a transition from the basic vitamins and minerals to whole food-based supplements, the fame of these basic ones is declining. The main reason is a growing innovation around whole food-based products, natural carotenoids and polyphenols, as well as the fact that most vitamins sold are synthetic.”
Preventive Health
Roughly 10,000 Baby Boomers turn 65 each day, and will continue to do so for the next 19 years, according to the Pew Research Center. As this large generation enters the “golden years,” many are utilizing dietary supplements, especially antioxidants, to preserve their heath.
“Our aging populations are increasingly aware of health risks and related preventable measures due to various public education campaigns, recommendations from physicians and nutritionists, and periodic scientific news,” noted Catherine David, product manager, Neptune Technologies & Bioressources Inc., Laval, Quebec, Canada. “There is a definite trend toward more proactive, preventive behavior on the part of consumers than previous reactive modifications in lifestyle changes following tardy diagnosis or treatment.”
Eric Ciappio, scientific leader of nutrition science and advocacy, DSM Nutritional Products, Parsippany, NJ, said antioxidant trends are highly correlated with the general consumer shift toward preventive health. Antioxidants are appealing due to their ability to reduce cell-damaging free radicals. “Antioxidants are said to have a whole array of health benefits,” said Mr. Ciappio, “most of which are believed to be long-term and cumulative, rather than promising a quick fix for an existing condition.” Anti-aging and the prevention of the eye disease macular degeneration, cancer and stroke are good examples of conditions that could benefit from antioxidant use long-term, he added.
Oxidative Stress
Antioxidants are essential to protecting the body from oxidative stress from free radicals, which Mr. Ciappio said, “are a byproduct of normal metabolism as well as certain environmental factors (e.g., cigarette smoke).”
An unbalanced diet, extreme exercising, modern lifestyle and air pollution can also contribute to oxidative stress for people in all stages of life, according to Algatechnologies’ Ms. Kat. “The DNA in every cell in the human body suffers about 10,000 ‘hits’ from free radicals each day. It is therefore very important for everyone to uphold a diet rich in antioxidants and to consume supplements with special antioxidants that are no longer readily available in our diet, such as natural astaxanthin.”
Combating exercise-induced oxidative stress is also an emerging trend. “Exercise produces a lot of free radicals in the mitochondria as a byproduct of converting glucose to energy,” explained Brien Quirk, director of R&D for the San Jose, CA-based Draco Natural Products. “Muscle damage from exercise causes inflammation, which results in free radical production. Antioxidants have been shown to improve muscle recovery time and lessen pain and inflammation following exercise.”
In addition, antioxidants support consumers looking to protect their skin from the harmful effects of free radicals, which he said “are known to damage the lipid membrane of skin cells, and contribute to wrinkles and the uneven pigmentation of skin.” Free radical production from UV and excessive light exposure to the retina can lead to macular degeneration of the eyes, he added.
Despite the many benefits of these free-radical scavenging nutrients, a recent New York Times blog post “Are Vitamin Drinks a Bad Idea?” suggested there can be too much of a good thing. According to the report, many functional beverages are offering vitamins and nutrients at levels well past the limits of safety established by the Institute of Medicine. In the case of antioxidant drinks—which are wildly popular and plentiful—an excess of antioxidants could be neutralizing too many free radicals. This may be problematic, as they are needed for some beneficial processes in the body, such as fighting off infection and cancer cells.
Cardiovascular Health
The World Health Organization reported that cardiovascular disease (CVD) is the leading cause of death globally, resulting in 17.5 million deaths in 2012. Antioxidants may benefit many health factors that lead to CVD, including blood pressure, cholesterol and circulation.
Interest in the benefits of antioxidants for heart health and blood pressure are strong drivers for this market, noted Neptune’s Ms. David. Antioxidant use for cardiovascular health, plus consumers’ interest in foods naturally rich in antioxidants, has contributed to the antioxidant market’s overall growth, she said.
“It is known that oxidized LDL cholesterol is more atherogenic (artery clogging) than when it is non-oxidized,” said Draco’s Mr. Quirk, noting antioxidant’s benefits for healthy cholesterol management.
Antioxidants from blueberries could emerge as an important ingredient for cardiovascular health, he added. “One phyto-compound with antioxidant effects that is growing in its market share is a phenolic known as pterostilbene, which is found in blueberries and has some benefits similar to resveratrol for cardiovascular health.”
Shaheen Majeed, marketing director, Sabinsa, East Windsor, NJ, suggested antioxidant products addressing healthy circulation and the reversal or prevention of atherosclerosis could help expand the antioxidant market, particularly in the U.S., Europe and China.
“Atherosclerosis was the number one health issue consumers tried to address with condition-specific dietary supplements in 2011, followed by lowering cholesterol and blood pressure. One-third (34%) of women and half (52%) of men have been diagnosed with significant plaque building up in their arteries thanks to improved imaging techniques that are now more commonly employed in diagnostic testing.” Additionally, Mr. Majeed said, “Circulation is now a bigger mass market opportunity than LDL or HDL cholesterol in 2012, according to Sloan Trends’ TrendSense.”
Inflammation
Arthritis and diabetes, two significant concerns for the aging population, involve inflammatory processes that generate extra free radicals, according to Mr. Quirk. Antioxidants, he said, have been shown to improve joint health by reducing inflammation caused by free radicals, and may also help to reduce blood sugar among diabetics.
Savvy Consumers
With health benefits linked to a wide array of conditions, consumers rely on antioxidant ingredients at all walks of life.
In 2013, HealthFocus International conducted a study that indicated a steady percentage of shoppers consistently want to see label information on antioxidants, with a spike in interest in 2008. Likewise, increased usage is more or less stable, with the exception of a surge in 2010. The study also revealed 40% of shoppers surveyed said that a “Good source of antioxidants is extremely/very important on labels,” and 20% said they “increased use of antioxidants over the past two years.”
Shoppers older than 50 felt most strongly about the importance of antioxidants on the label (45% in their 50s and early 60s and 44% 65-plus); the study also showed an increase in antioxidant usage was highest among men (24%) and highest earners (24%) and lowest among the oldest shoppers (14%).
As a result of numerous age-related health issues, older consumers are a clear and powerful consumer base. “The aging population, consisting of Baby Boomers with disposable income, is still the main buyer of antioxidants,” commented Mr. Wuagneux of RFI.
Pete Maletto, president and senior scientist, PTM Food Consulting, Point Pleasant, NJ, said this mature and educated audience is looking to prolong good health with a variety of new products targeting multiple health concerns. “New-age food-based antioxidants possess amazing anti-inflammatory benefits that far outreach the basic free radical scavenging vitamins of the 1980s and 1990s.”
Mr. Majeed said interest in cognitive health among aging consumers is a key market driver. “In the top 10 most important health issues, three involve brain health/mental acuity, memory and mental agility. Twenty-seven percent of consumers purchased antioxidant-containing foods that they believe will affect mental acuity and memory in 2010. Lack of mental acuity is in the top three U.S. health concerns. This may be due to the fact that 80% of consumers surveyed had one or more relatives who suffered from Alzheimer’s, Parkinson’s or senility. Antioxidant supplements should be formulated to take advantage of this trend.”
In general though, the overall consumer shift toward healthier, less processed and nutritious foods are leading more consumers to antioxidants. Mr. Liu of SeabuckWonders said, “More people want to adopt healthier habits and are more aware of natural remedies for battling disease. This awareness is due in part to availability of nutritional information growing and more coverage by experts in popular media (Dr. Oz for example).” He pointed to the growth of the alternative diet market, including groups like vegans and paleo-diet followers, bringing a whole new crop of consumers to push the antioxidant market forward.
Emerging Antioxidants
The strong body of science validating beta-carotene, vitamin C and vitamin E has led the U.S. Food and Drug Administration (FDA) to qualify these three ingredients as the only antioxidants to be used in labeling and nutrient content claims, noted Rachel Murphy, scientific leader, nutrition science and advocacy, DSM. Therefore, these three vitamins are primarily used in fortification of foods and beverages, such as fruit juices and cereals, she said. Fortification is an important way to fill the nutritional gaps for consumers deficient in antioxidants. “From a nutrient perspective, there are large gaps in dietary intake of antioxidant vitamins; over 93% of adults in America do not meet the estimated average requirements for vitamin E, and over 50% do not meet recommended intakes for vitamin A and C.”
DSM’s Mr. Ciappio commented that these more established and popular antioxidants, particularly vitamins C and E, are often “underappreciated despite the tremendous and still growing body of literature supporting their role in human health.”
For example, he pointed to the results of a major clinical trial published in the Journal of the American Medical Association (JAMA) in 2014, which demonstrated the role of vitamin E in slowing the progression of Alzheimer’s disease. He added, “Data from national surveys show that people do not get enough vitamin E or vitamin C in their diets, so for many it makes sense to consider using a dietary supplement or fortified food that contains these antioxidants to help meet their nutritional needs.”
While food fortification can help to improve consumer nutrition, there are many common foods naturally rich in antioxidants that are backed by sound clinical research. For example, Mr. Ciappio pointed to olive oil, which is a staple in the Mediterranean diet and has been linked to heart health for more than 60 years. However, he said, “it was only recently established that antioxidant polyphenols found within olive oil, such as hydroxytyrosol, can protect blood lipids from oxidative damage and help maintain heart health. This science was so compelling that the European Food Safety Authority (EFSA) authorized a health claim for hydroxytyrosol in 2011.”
In addition, he said spinach and eggs contain antioxidant carotenoids lutein and zeaxanthin, which have been shown to support eye health by absorbing damaging blue light that enters the eye. He also cited research published in Nutrition Review (2014) that demonstrated a link between these nutrients and brain health.
Mr. Pond of FutureCeuticals said his company is researching numerous fruits and vegetables with a range of ORAC scores (oxygen radical absorbance capacity), and observing in vivo changes of various free radicals in the blood. “Our research indicates substantial antioxidant benefits for certain natural products when used at optimal dosages. Dose response and bioavailability are critical keys to having a proper understanding of any antioxidant value and, more importantly, any activity of a product in vivo.”
In its research on the free radical scavenging activity of fruits, vegetables and grains, Mr. Pond said FutureCeuticals is “regularly seeing a bell curve effect whereby, above a certain level, antioxidant materials actually become pro-oxidative.” Proper antioxidant science often involves careful consideration of the correct dose for a given category of phenolic compounds. “We are using short-term (acute) dose response studies in order to substantiate bioavailability either directly by quantitative analytical procedures, or indirectly by function, as observed under properly controlled conditions in the acute setting, as is appropriate for natural products.”
Late in 2014, FutureCeuticals published a human clinical study that showed effects of its Spectra natural supplement on changes in oxidative and nitrosative stress markers in vivo. The study determined that a 100 mg dose actually yielded the best in vivo effect. “Interestingly, the results also indicated a spike in nitric oxide and increased oxygen utilization after ingestion of Spectra,” noted Mr. Pond.
Mr. Raz, of LycoRed, predicted targeted combinations of antioxidants could be the next trend in the market. “While in the past, single-sourced antioxidants were broadly used (vitamin C, vitamin E, beta-carotene and others), advanced scientific research indicates specific compositions that combine several antioxidants at an optimized dosage may drive a much more powerful effect.”
As a result of this ongoing area of research, more product introductions based on combinations of whole fruits and vegetable extracts have emerged. “Combinations made of tomatoes, berries, cocoa, algae, grapes and other whole foods are being studied and commercialized for indicating specific targets, including cardiovascular health, vision health, prostate health, anti-aging, sports recovery and many more.”
An emerging star in recent years, turmeric is garnering significant attention. PTM’s Mr. Maletto said turmeric/curcumin is an excellent antioxidant linked to life extension.
Nutrition Business Journal projected turmeric/curcumin would be among the top 10 best-selling supplements through 2016, virtually doubling in sales from $103 million in 2013 to $235 million, with a CAGR of 21.5%.
Mr. Maletto attributed growth to extensive research backing the inhibition of cancer, arthritis, diabetes, cardiovascular disease, osteoporosis, and potentially reversing the pathological processes underlying Alzheimer’s disease. For example, curcumin may reduce deadly beta amyloid plaques in the brain. It may also assist the liver in processing viruses such as hepatitis, and other conditions.
Additionally, he said one of curcumin’s most important mechanisms of action is “its ability to inhibit activation of the transcription factor, nuclear factor-kappa B (NF-kB), a potent inducer of chronic inflammation. NF-kB is a protein that acts as a sort of switch, turning inflammation on by activating genes involved in the production of inflammatory compounds. As NF-kB activation has been implicated in all the stages of carcinogenesis, this transcription factor is a potential target in cancer prevention and is the subject of intensive research.”
Switzerland-based Frutarom BU Health’s technical specialist, Eden Beth, said antioxidants derived from caffeine-containing botanicals such as green tea, yerba mate and coffee are known to be naturally rich in beneficial compounds. These antioxidant-rich ingredients are being utilized in “dietary supplements and increasingly in functional foods and functional beverages—ranging from sophisticated instant beverages to RTD (ready-to-drink), single shots and premium, niche bottled coffees.”
“Yerba mate and other South American herbs used for teas and in beverages often will have high levels of naturally-occurring antioxidants in the form of flavonoids—or more generally characterized as polyphenols. As one example, Yerba mate (Ilex paraguariensis) such as Frutarom’s Finomate is tested for different compounds and is a naturally antioxidant-rich plant.”
Alpha-lipoic acid (ALA) and astaxanthin are two unique antioxidants that have recently emerged in the supplement market, according to Neptune’s Ms. David. “ALA is usually sold under its own name, whereas astaxanthin can be found either as a standalone product or within marine sources like omega-3 krill oil.”
What makes ALA unique, she said, is that it functions in water and fat (unlike some more common antioxidants) and it appears to be able to recycle other antioxidants after they have been used up. As for astaxanthin, Ms. David explained, “it is one of the most powerful antioxidants; it is bioavailable throughout the body and is quite potent when compared to other antioxidants. Astaxanthin has been shown to reduce oxidative stress, which is believed to be the main cause of cellular aging.”
The astaxanthin found within krill oil also helps “stabilize liposomes in the body that protect important fatty acids from degradation by harsh stomach acids, which in turn allows more of them to be absorbed by the body. This powerful antioxidant provides exceptional protection against oxidation, greatly extending the life of the product,” she said.
AstaReal, Inc., Burlington, NJ, offers AstaREAL natural astaxanthin. Technical support with the company, Janice Brown, said consumers are becoming more aware of astaxanthin as an alternative to traditional antioxidant sources.
Discussing the potency of AstaReal, she cited research published in Carotenoid Science in 2007. “Studies show AstaREAL natural astaxanthin to be 6,000 times stronger than vitamin C at ROS (reactive oxygen species) quenching. The same study indicated AstaREAL natural astaxanthin to also be 800 times stronger than CoQ10 and 40 times stronger than beta-carotene.”
Ms. Kat of Algatech noted that the growth of astaxanthin has much to do with the depth of research validating the overall carotenoid category. “Carotenoids are very powerful antioxidants; they absorb light due to their special bonding structure, and hence provide defense from excessive light radiation and photo-oxidative damage,” she explained.
AstaPure astaxanthin has also been shown in multiple studies to assist in protecting the body under stress conditions, she said. It is widely used in formulations related to brain function, sports activity, skin health and more.
Mr. Kaiser of Natreon said that PrimaVie shilajit is an important emerging ingredient for the company. “With an ORAC rating as high as many superfruits, PrimaVie is an ancient Ayurvedic ingredient used for thousands of years. Using modern clinical and animal research, Natreon has shown PrimaVie functions as a mitochondrial antioxidant, restoring ATP and boosting energy.”
The superfruit craze still holds weight in the antioxidant market, according to Mr. Liu of SeabuckWonders, who said these ingredients have dominated the category for the last five years, with new introductions to the group each year. “Some big ones to look out for are amla and sea buckthorn,” he said, as well as pterostilbene.
Flavonoids have the capability of chelating certain trace elements such as copper and ferrous iron so that they won’t generate toxic hydroxyl radicals, according to Draco’s Mr. Quirk, “Many of the flavonoids found in green tea, blueberries and other anthocyanin rich foods have this effect and help to protect cell membranes and cholesterol from being oxidized.” Fruits and vegetables contain an abundance of flavonoids that reduce LDL oxidation, free radicals generated by inflammation, and free radicals from reactions with copper and iron ions, he added.
Mr. Majeed of Sabinsa said that pomegranate juice and blueberries are the fastest growing antioxidant-containing fruits and fruit products. “Mangosteen, goji berry and acai had the highest superfruit sales in 2012. Passion fruit, guava, paw paw and dragon fruit were the best-selling superfruits in 2011,” he said.
He also noted that cocoa and other chocolate-containing products are generating consumer awareness on par with antioxidants and vitamins. “Polyphenols and flavonoids remain the strongest phytochemical mass market ingredients,” he said. “Spices, chick peas, lentils, seeds and nuts are among the hottest new super foods containing antioxidants.”
Changing Tides
Despite the many antioxidants gaining consumer attention, some of the traditional offerings in this space have seen a decline for a variety of reasons.
Beta-carotene, for example, has lost some favor with consumers, according to Draco’s Mr. Quirk, as a clinical study reported smokers taking extra beta-carotene had an increased risk of lung cancer. He also cited studies demonstrating that “selenium supplementation may increase the risk of diabetes,” as a deterrent for the use of this ingredient. “Vitamin E has come under scrutiny in some studies that have shown increased rate of death from all causes at supplementation of 400 IU of alpha tocopherol,” Mr. Draco said. “Some have theorized that taking only extra alpha tocopherol causes a deficiency of the form of vitamin E known as gamma tocopherol, which is vital for quenching specific free radicals (i.e., peroxynitrate radicals).”
Mr. Pond of FutureCeuticals pointed to a dip in superfruit interest, suggesting better science was needed in some cases. “Antioxidants, including some superfruits, that simply have high ORAC levels, but lack extensive human clinical studies, have lost some of their initial appeal to consumers.”
Natreon’s Mr. Kaiser said mature antioxidants like vitamins E and C, and antioxidant minerals have plateaued. “There is a great deal of media skepticism as to the long-term health benefits, and the VMS [vitamins, minerals, supplements] industry hasn’t been effective at refuting the negative press.”
“The worst hit in recent years has been isolated vitamin E supplements,” noted Mr. Liu of SeabuckWonders. “One study, which followed subjects regularly taking vitamin E showed that there were no benefits over a course of nine years. Though some say this study was flawed, the study was publicized and consumers listened.” He cautioned that consumers are taking notice when an ingredient gets bad press.
DSM’s Mr. Ciappio said the antioxidant meso-zeaxanthin has also come under some scrutiny. Meso-zeaxanthin, he said “is a metabolic byproduct of the important antioxidant lutein that accumulates in the eye. It is not naturally found in the food supply in appreciable amounts, but can be present in certain lutein/zeaxanthin dietary supplements (often labeled in the ingredient line as ‘zeaxanthin isomers’).” In 2014, the use of supplemental meso-zeaxanthin was linked to a skin condition known as toxidermia in France, Mr. Ciappio said. In light of these findings, he cautioned against using supplements containing this substance until more research and testing is done to prove its safety.
Sound Science
There are a variety of scientifically validated testing methods to ensure the efficacy and potency of antioxidant supplements—the most common being ORAC value, noted Mr. Maletto of PTM. This test, he said “attempts to quantify the ‘total antioxidant capacity’ (TAC) of a food by placing a sample of the food in a test tube, along with certain molecules that generate free radical activity and certain other molecules that are vulnerable to oxidation. After a while, they measure how well the sample protected the vulnerable molecules from oxidation by the free radicals. The less free radical damage there is, the higher the antioxidant capacity of the test substance.”
Mr. Pond said FutureCeuticals has a unique perspective on testing methodology for antioxidants, “as we have been intimately involved with the development and evolution of ORAC, ORAC-FN, and now the next logical step: detecting antioxidant activity real-time within the human body. Dr. Boris Nemzer, FutureCeuticals director of R&D and quality assurance, worked closely with Dr. Boxin Ou and Brunswick Labs at the very beginning of the ORAC development, and also with subsequent improvements and expansions to antioxidant potential testing.”
Ensuring these antioxidants reach the bloodstream is another matter that must be examined, according to RFI’s Mr. Wuagneux. He said ORAC testing can be done on blood, which RFI did with its OxyPHyte Ultra Blend more than 10 years ago.
“A newer, more relevant form of antioxidant testing is plasma antioxidant capacity whereby a test substance is administered in vivo to a human volunteer to see how well it increases the antioxidant capacity in the blood and takes into account the absorption of a test substance,” noted Mr. Quirk. “Since only 5% of some flavonoids such as EGCG (Epigallocatechin gallate) and quercetin are known to be absorbed, it does not make sense to test these substances in a traditional test tube assay (in vitro) as with the older ORAC method, because it would not be an accurate indication of how well utilized the antioxidant source is.”
Algatech’s Ms. Kat pointed to antioxidant testing methods that “have been approved by pharmacopeias around the world such as ET-based (electron transfer) or HAT-Based (hydrogen atom transfer), represented by the ORAC assay.” This evolving technology, she said, has advanced antioxidant methods for more accurate results, but also discredited ineffective compounds. For example, she explained “it’s possible to determine the purity of astaxanthin by using HPLC (high-performance liquid chromatography).”
In addition to ORAC, Mr. Liu explained many other assays have been developed, such as ORAX or PAOXI, which measure antioxidants in different ways. “Nowadays, many researchers think that it is much wiser to combine ORAC’s different versions (there are three) with other assays to get a more complete understanding. They refer to this as RACI or relative antioxidant capacity index.” An additional assay is the CAA, which was introduced around 2007. This method, Mr. Liu said, included a clearer picture of antioxidant metabolism than was previously available. Lastly, he explained that CAP-e is an assay that is especially important because it can measure the bioavailability of antioxidants. He noted, however, “Many of the assays have come under scrutiny, including ORAC. The methods used, and our understanding of how antioxidants work, are constantly evolving.”
