Antioxidant research update: Polyphenols, resveratrol, lycopene, lutein, and tocotrienols

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The antioxidant market is rapidly growing, and this growth is driving important changes in the way antioxidant ingredients are formulated and marketed. Lower manufacturing costs and higher consumer demand for natural products are expected to ultimately drive the global antioxidant supplement market to a USD $4.5 billion valuation by 2022, up from USD $2.9 billion in 2015, per Allied Market Research.¹

As this market growth opens up new opportunities for antioxidant brands and manufacturers, expect consumer needs and ingredient research to influence how brands will successfully develop and market antioxidant supplements. Here are just some of the ways that the antioxidant market-and antioxidants themselves-are evolving.

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Resveratrol Performs Unique Functions among Antioxidants

David Tetzlaf, senior marketing manager at Evolva (Reinach, Switzerland), says that resveratrol is unique among antioxidants in that it targets a number of proteins and has mechanisms of action beyond just preventing oxidation. Tetzlaf points to recent studies that confirm resveratrol’s role in activating mitochondrial biogenesis and increasing bone density. Evolva’s Veri-te resveratrol ingredient, he says, is ideally positioned to meet consumer demand for antioxidant ingredients that also have a broader impact.

Says Tetzlaf: “Preclinical and clinical studies have documented a number of direct protein activity improvements. Resveratrol targets SIRT1 (sirtuin 1) and AMPK (adenosine 5’ monophosphate-activated protein kinase), for example, which are both important factors in healthy aging. AMPK is also one of the main gatekeepers involved in cellular glucose uptake. Other studies emphasize further protein interactions such as activation of nitric oxide synthase. These additional functions make resveratrol a unique ingredient in a crowded field of other antioxidants.”

Researchers are still unraveling the many ways that resveratrol affects human health. At an event called the Resveratrol 2018 conference in Xi’an, China, it was announced that resveratrol has vasoactive properties that can stimulate cerebrovascular function and reduce the perception of pain. Tetzlaf says that resveratrol may also have bearings on gut health and oral health, as it exhibits selective antibacterial properties that make it desirable for such targeted applications.

Tetzlaf says that while consumer awareness of antioxidants is high, the broad array of products on the market can be confusing. He notes that the affluent baby boomer market in particular is looking for more specific solutions around the wellness concerns that matter most to them, and are searching for clinical evidence to back up product claims.

Shaheen Majeed, president, worldwide, of Sabinsa (East Windsor, NJ), says that resveratrol may hold promise as an exercise supplement due to its antioxidant properties. He cites the results of a Sabinsa-sponsored study involving Sabinsa’s branded resveratrol ingredient, Resvenox. The study², a double-blind, placebo-controlled clinical trial, followed 16 healthy young adults for four weeks and tracked their mitochondrial performance during low-intensity exercise. Participants received either 1000 mg of Resvenox and 20 mg of BioPerine brand piperine (n=8), or a matching placebo (n=8), daily for the duration of the trial. Participants completed three sessions of submaximal endurance training per week, focusing on the wrist flexor muscles in the participants’ non-dominant arms. Participants’ dominant arms were used as a control for the training effect.

The study authors tracked mitochondrial capacity using near-infrared spectroscopy and found statistically significant differences in mitochondrial capacity between the resveratrol/piperine group and the control group. The resveratrol/piperine group saw a 40% increase in mitochondrial capacity, relative to a 10% increase in the control group. Neither group exhibited changes in mitochondrial capacity in the untrained arm. 

While consumers are already quite familiar with antioxidants in their traditional applications, Majeed says that increased clinical substantiation is motivating further market diversification. “Antioxidants neutralize free radicals and prevent damage to cells. But recent research suggests that antioxidants may have more profound and specific effects on the body than was previously thought, playing a significant role in aging, immune support, eye health, joint support, and blood sugar support. Because of this increased understanding, antioxidant supplements are more personalized and targeted than ever before.”

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Lycopene Gains More Validation as a Skin Health Supplement

Antioxidants in general are seeing broad acceptance in the mainstream and alternative health and wellness communities. Golan Raz, head of the global health division at Lycored (Secaucus, NJ), says that antioxidants enjoy an important benefit: Simplicity.

“Consumers feel knowledgeable enough about antioxidants to add these ingredients to their diets,” Raz says. “We’re also seeing an interesting expansion in the kinds of delivery systems being used, with bars and beverages often utilized as delivery platforms.”

Lycored recently reported the results of a newly published clinical trial³ examining the efficacy of Lycoderm, Lycored’s carotenoid-rich tomato nutrient complex with rosemary extract. The study found that supplementation with the nutricosmetic Lycoderm supported skin’s resilience to UV rays. The randomized, double-blind, placebo-controlled multicenter study included 149 healthy volunteers who were randomly assigned to take either Lycoderm or placebo for 12 weeks, followed by a five-week washout phase. Results showed that supplementation with the tomato nutrient complex significantly protected subjects against UVB-induced erythema formation compared to placebo. It also protected against UVB-induced upregulation of interleukin-6 and tumor necrosis factor-alpha when compared to placebo.

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Consumers Turn to Lutein for Antiaging, Cognitive Health

An aging baby boomer population and a growing knowledge economy workforce have created demand for supplements that preserve cognitive health and general vitality. Ceci Snyder, global vision product manager for Kemin (Des Moines, IA), says that lutein’s role as an antioxidant makes it ideal for branding and positioning in these verticals.

“Consumers are becoming more engaged and motivated to improve their health,” Snyder says. “An aging population of baby boomers eager to stay active, younger Americans looking for healthier dietary choices, and a growing knowledge of how antioxidants work are all driving growth in antioxidants.”

Snyder also notes that cognitive health is a growing area of consumer interest for antioxidants. Consumers are looking for brain health supplements with a proven track record, and high-quality clinical trials will give consumers confidence that they’re opting for supplements that work.

For instance, “Cognitive health is an exciting area of new research with [Kemin’s branded] FloraGLO lutein,” Snyder says. “In one randomized, double-blind, placebo-controlled clinical trial, increased macular pigment optical density was found to be related to improved visual memory, complex attention, and reasoning ability.”

The study⁴ Snyder references followed 51 healthy young adults between the ages of 18 and 30. Subjects received 10 mg of FloraGLO lutein and 2 mg of zeaxanthin per day (n=37) or a matching placebo (n=14) for 12 months. The participants were assessed for serum lutein and zeaxanthin concentration, verbal memory, visual memory, reasoning ability, executive function, complex attention, and cognitive flexibility at baseline and after 12 months. After controlling for practice effects, the researchers found a statistically significant improvement in cognitive performance in the experimental group.

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Antioxidant Vitamins Go Clean-Label

The clean-label trend has penetrated the antioxidants niche, particularly with respect to vitamins. Consumers-specifically Millennial consumers-are looking for more than just the lowest-price brand.

Saumil Maheshvari, marketing analyst for Orgenetics (Brea, CA), says that antioxidant vitamins are going up-market. “The antioxidant market may be following suit with the vitamin/mineral category, moving down the whole-food and USDA-organic route. The reason for that could be the increasing consumer awareness about clean labels and clean supply chains.”

Maheshvari says that consumers have started connecting the dots regarding antioxidant research and are looking for ways to supplement a diet that may not be very rich in antioxidants. As the antioxidant space continues to grow, Maheshvari expects consumer education to become a priority.

“One of the challenges of marketing antioxidants is that there are so many different types,” he says. “These antioxidants can have different effectiveness, and the use of ORAC values has been up for a bit of a debate. It depends on which antioxidant is prevalent in the product, as different antioxidants may have different properties.”

Orgenetics has followed the clean-label trend with its own products. Orgenetics’ branded Orgen line of vitamin-based antioxidant supplements has been standardized to ensure a consistent dosage, and the company uses water-based extraction to avoid contaminating ingredients with harmful solvents or excipients.

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Tocotrienol for Bone Health

One product category that antioxidants may not have traditionally been considered to occupy is bone health, which is what makes data on antioxidant ingredients like resveratrol so exciting. New research is also showing that certain vitamin E antioxidants can help promote bone health in a variety of ways.

Anne Trias, product director for American River Nutrition (Hadley, MA), says that while alpha-tocopherol vitamin E has long been prominent in the antioxidant space, the other family of vitamin E ingredients, tocotrienols, are now showing even more promise for a variety of applications. Delta-tocotrienol, in particular, Trias says, appears to be the most bioactive of the vitamin E group.

Says Trias: “Antioxidant studies have found that tocotrienols are much more potent antioxidants, by about a factor of 50, than alpha-tocopherol. Of the tocotrienol isomers, delta-tocotrienol is the most active due to its preferable molecular makeup. Delta-tocotrienol isn’t a common vitamin in the Western diet, but a high concentration of it can be found in annatto, a plant whose extracts are used for food coloring.”

American River’s branded DeltaGold tocotrienol ingredient has been shown in studies to be particularly effective as a bone health supplement. One randomized double-blind placebo-controlled clinical trial⁵ followed 87 postmenopausal women (average age 60) with lower-than-average bone density for 12 weeks. Participants were randomly assigned to receive either 860 mg (n= 30) or 430 mg (n= 29) of DeltaGold brand tocotrienol per day, or a 430 mg placebo made from olive oil (n= 28), for 12 weeks. Study authors measured participants’ bone mineral density, vitamin D concentrations, and thyroid-stimulating hormone concentrations at baseline, week 6, and week 12. The study found that tocotrienol supplementation decreased bone resorption and improved bone turnover rate. The authors hypothesize that tocotrienol’s osteoprotective effects may be a result of its antioxidant properties.

Trias says that antioxidants have become synonymous with antiaging given that many aging processes are linked to oxidative stress. Older consumers, she says, are a strong market for antioxidants: “A 2018 consumer survey commissioned by the Council for Responsible Nutrition showed that 78% of adults over age 55 take dietary supplements, and the main reasons for supplementation included bone health, heart health, and healthy aging. Antioxidants play a role in all three of these categories, and older adults are likely to turn to formulations addressing these concerns first.”

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Antioxidants in 2019

Expect the industry trends that have influenced other popular ingredient markets to continue changing the antioxidants market as well. Tetzlaf says consumers are looking for two things from antioxidant brands: Honest marketing and an easy-to-use format. Consumer demand for transparency will mean clean-label brands will perform best, while busy lifestyles will open up opportunities for convenient product formats like powders, gels, and stick packs. Antioxidants play many roles in human health, but consumers are looking for solutions to specific problems, which means product positioning and specificity matter.

Sidebar 1: Polyphenols Boost Antioxidant Reserves in Healthy Adults

Polyphenols have long been known to have in vitro antioxidant capabilities, but their efficacy in vivo was called into question 10 years ago, when certain research indicated the human body synthesizes enough polyphenols on its own to meet most people’s wellness needs.⁶ Now, though, new research has demonstrated that polyphenol supplementation does indeed boost plasma antioxidant levels in healthy adults. A randomized, placebo-controlled, double-blind crossover trial⁷, first reported in an October 2018 press release by Fytexia (Vendres, France) on the company’s unique Oxxynea polyphenol ingredient blend, showed that polyphenol supplementation increased antioxidant defense and reserve capacity. This makes polyphenols a potentially important supplement for adults who may not eat enough fruits and vegetables in their diet.

Poor Consumer Diets Create Market Opportunities

Laure Nogier, marketing project manager for Fytexia, says that changing consumer lifestyle habits are opening up opportunities for supplement brands in the antioxidant space. Fruits and vegetables are the richest dietary source of antioxidants, Nogier says, particularly in the case of polyphenols. But with most consumers eating less than the World Health Organization’s daily recommended intake of 400 grams of fruits and vegetables, most consumers aren’t getting enough polyphenols from diet alone to meet their antioxidant needs.

“Knowledge of phenolic compound metabolization and bioavailability has helped us develop an innovative formula for bioactive polyphenols within the main sub-families of phenolic compounds,” Nogier says. “The concept of [supplement-to-whole-food] equivalence is a friendly concept for consumers that helps them meet their dietary needs, which is why Oxxynea 5-a-day is recommended at a dosage of 450 mg per day to equal five servings of fruits and vegetables.”

Nogier says antioxidants are gaining popularity for a number of reasons. Consumers are looking for health maintenance products that can fend off free radicals accumulated by any number of daily lifestyle factors, such as pollution, UV exposure, or lack of physical activity. Nogier notes that word antioxidant is well understood by consumers, and a number of brands are now narrowing focus on particular kinds of antioxidants like polyphenols, which appeal to an audience looking for plant-based solutions.

Sidebar 2: Studying Antioxidant with Physics

The worlds of nutrition and physics are about to collide as researchers examine antioxidants from both angles. Recently, Osaka University professor Kazuo Kobayashi (Osaka, Japan) conducted a series of experiments that involved using a linear electron accelerator, or LINAC, to shoot electrons at water molecules, causing the molecules to produce free radicals. Kobayashi said in a press release that his experiment has proven that LINACs are a valuable tool for biological research, and this opens up new avenues of study for biologists and other professionals who research antioxidants for a living.⁸

References:

1. Prasad E. “Antioxidants market by type, natural (Vitamin A, Vitamin B, Vitamin C, and Rosemary Extract), synthetic (butylated hydroxyanisole, butylated hydroxytoluene, and others) – Global opportunity analysis and industry forecast, 2014-2022.” Allied Market Research. Published online December 2016.
2. Polley KR et al. “Influence of exercise training with resveratrol supplementation on skeletal muscle mitochondrial capacity.” Applied Physiology, Nutrition, and Metabolism, vol. 41, no. 1 (January 2016): 26-32
3. Groten K et al. “Tomato phytonutrients balance UV response: results from a double-blind, randomized, placebo-controlled study.” Skin Pharmacology and Physiology, vol. 32, no. 2 (March 2019): 101–108
4. Renzi-Hammond LM et al. “Effects of a lutein and zeaxanthin intervention on cognitive function: A randomized, double-masked, placebo-controlled trial of younger healthy adults.” Nutrients, vol. 9, no. 11 (November 2017): 1246-1258
5. Shen CL et al. “Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: A 12-week randomized double-blind placebo-controlled trial.” Osteoporosis International, vol. 29, no. 4 (April 2018): 881-891
6. Starling S. “Veteran researcher: Polyphenols don’t work as antioxidants in vivo, but…” Nutraingredients.com. Published online July 11, 2010.
7. “Fytexia launches a new grade of Oxxynea supplying clinically proven bioavailability and demonstrated efficacy in counteracting oxidative-stress in vivo.” Fytexia website. Published online October 18, 2018
8. Obayashi S. “Electron accelerators reveal the radical secrets of antioxidants.” EurekAlert/American Association for the Advancement of Science. Published online March 19, 2019.