A Deeper Look Into Antioxidants
Antioxidants
Antioxidants innovations intrigue manufacturers and suppliers for what is to come.
Antioxidants, which according to MedlinePlus are “man-made or natural substances that may prevent or delay some types of cell damage.”
This cell damage is caused by free radicals and when they accumulate, that is when oxidative stress can become a problem.
While antioxidants offer effective benefits in finished products—manufacturers and suppliers are innovating to make these products even more appealing, especially to the end consumer.
Innovation is Key
While antioxidants can be derived from various synthetic sources, more consumers are looking for a natural approach to their health.
“I think that consumers are really gravitating to natural sources of antioxidants,” explained Rachel Kreider, MPH, RD, LDN, manager of business development for Boundary Bend Wellness (California), which offers olefresh, an olive leaf extract formulation. “Lab synthesized compounds are still out there, and have a place in certain types of formulations, but if you can get great antioxidant and other health benefits from nature, why would you use a man-made source? It also seems like consumers are starting to understand that all botanicals are not created equal, and that you should really know and trust your company and their manufacturing to ensure that you are getting a truly traceable, quality product.”
Shaheen Majeed, president worldwide, Sabinsa (New Jersey), agreed. “Formulators select specific antioxidants based upon their activity or the desired functional outcome, such as a preservative, to reduce the oxidative spoilage of food, or as an antioxidant supplement.” He added, “The most popular antioxidants in finished products are vitamin C, vitamin E and beta carotene. They’re generally favored because they are relatively stable, readily available, safe, natural and less reactive to the food components. And as delivery systems expand to gummies, functional foods, beverages and other alternative forms, suppliers are innovating new ways to meet these demands.”
Florida-based HP Ingredients offers the citrus ingredient, MaquiBerry, a branded form of maqui berry (Aristotelia chilensis).
“Of all the berries,” noted Annie Eng, CEO, “MaquiBerry is quickly gaining interest among consumers who want more choices than typical bilberry, blueberry and cranberry. Maqui berry is the highest known antioxidant superfruit, with the highest ORAC (oxygen radical absorbance capacity) value (27600), containing high concentration of polyphenols and anthocyanins. Anthocyanins are the most powerful antioxidant compounds with the strongest benefits toward whole health, exhibiting health support of inflammation-based issues. Anthocyanins are known to neutralize enzymes that can destroy connective tissues, promote cardiovascular health by preventing oxidation of low-density lipoproteins (LDL), protect blood vessel walls from oxidative damage and support healthy blood glucose levels. Anthocyanins in MaquiBerry are unique, as 80 percent of all anthocyanins in MaquiBerry are delphinidin, the most important anthocyanidins found in dark berries. Delphinidin is reported to exert superior antioxidant and anti-inflammatory effects.
“Citrus ingredients are also considered as powerful antioxidants, and for good reason,” she continued. “But it’s more than just orange and vitamin C! For example, an Italian citrus, bergamot, has a distinctive antioxidant profile. The juice and albedo of bergamot has a unique profile of flavonoid and glycosides, including naringin, neohesperidin, neoeriocitrin, rutin, melitidin and brutieridin. Naringin has been shown to be beneficial in animal models of atherosclerosis, while neoeriocitrin and rutin have been found to exhibit a strong capacity to prevent LDL from oxidation. Importantly, bergamot juice’s brutieridin and melitidin [have been discovered] with an ability to inhibit HMG-CoA reductase.”
While antioxidants’ appeal is obvious for human health, their benefits to animals has driven growth.
“Anti-aging is a big buzzword today, especially among Baby Boomers, and in addition to seeing an increase in antioxidant supplements for inflammation support and heart, eye and brain health, the cosmetic industry is also jumping on board by adding various natural antioxidants, such as vitamins, carotenoids, polyphenols, flavonoids and stilbenes/lignans as to provide consumers with healthy aging creams and serums,” said Morris Zelkha, CEO of Israel-based TriNutra who offers ThymoQuin 3%, nigella sativa (black seed) oil (NSO) that has been standardized to 3 percent thymoquinone. “Apart from human supplementation, there has also been growth in the use of antioxidant ingredients in animal feed to promote growth and reduce diseases in poultry, cattle and pigs.”
As for FutureCeuticals (Illinois), the company has Spectra, which according to Andrew Wheeler, vice president of marketing for this business and Van Drunen Farms, “goes beyond antioxidant potential and demonstrates a new frontier in antioxidant science by documenting real, antioxidant action in the human body. A blend of natural ingredients, Spectra has been scientifically shown to inhibit free radical production, optimize cellular metabolism and increase nitric oxide levels within the body.”
More Benefits
When creating these products for consumers, manufacturers look for ingredients that not only address typical antioxidant benefits, but a wider range of health concerns, as well.
“Though there is strong awareness among consumers about the benefits of antioxidants, they are also seeking ingredients that have an even broader impact on health,” suggested Sally Aaron, senior vice president, health ingredients and marketing, Evolva (Switzerland). “For example, the benefits of resveratrol go beyond its performance as an antioxidant, with its mechanisms of action extending to a cellular and systemic level.
“Secondly, we believe consumers are interested in learning about the science and clinical studies that back any health claims,” Aaron added. “Our aim at Evolva is to offer more transparency and education around clinical trials, which go hand in hand with the marketing of antioxidants.”
Scientific research, or lack thereof, is a common theme, as its importance cannot be overlooked.
“There are many products on the market featuring claims that seem too good to be true with lack of scientific research to back them,” said Sébastien Bornet, vice president of global sales & marketing at Switzerland-based Horphag Research (exclusive global supplier of Pycnogenol and Robuvit). “Antioxidant supplements need to be held to a high standard to assure quality and high antioxidant content. With 40 years of research and more than 420 scientific publications, it has been shown that Pycnogenol is safe and effective. It is recognized as the most versatile ‘super-antioxidant’ with a broad range of health benefits.”
Further, manufacturers are paying extra attention to the supply chain process, making sure the items/ingredients meet the proper safety requirements.
“I absolutely love that manufacturers are placing more of an emphasis on supply chain,” Kreider expressed. “Botanical sources of antioxidants can be really powerful, but botanical ingredients require special care and attention as there is so much potential for adulteration or raw materials that do not meet spec. The test methods can be challenging, so customers need to really know that their manufacturer and their quality programs/raw material suppliers are top notch.”
Global Reach
Given the various benefits that antioxidants have to offer, the aging masses will see the antioxidant market heading in a positive direction.
“The use of antioxidants is very basic to each and every one of us, as we all are destined to age,” explained Anne Trias, product director, Massachusetts-based American River Nutrition. “Our most elemental building blocks—the body’s 30 to 40 million cells—are prone to oxidation, particularly the lipids contained within cell walls. Oxidation becomes a greater concern to the elderly population, as chronic conditions begin to take hold with advanced age. Although the world population continues to grow, older adults with greater antioxidant requirements are tipping the scales when it comes to projected age demographics. A U.S. Census Bureau report predicts that older adults will outnumber children for the first time between the years 2030-2035, with one demographer noting that by 2035, there will be 78.0 million people 65 years and older compared to 76.7 million under the age of 18.1 These trends suggest that antioxidants are here to stay, and demand will increase with the expanding aging population.”
In fact, according to Zelkha, the global antioxidants market is expected to reach $4.5 billion by the year 2022 (Allied Market Research). He also noted that “research continues to discover more extensive benefits from a large variety of antioxidants and formulators are finding more uses for food, beverage and other applications. We will continue to see growth in the antioxidant ingredient market as they play a leading and complementary role in healthy aging products.”
Nonetheless, even with the compound annual growth rate (CAGR) demonstrating growth, there is some confusion in terms of how products vary from one another.
“The state of the antioxidant market is very promising, as consumers are more aware than ever about the benefits of antioxidants to combat the damaging effects of free radicals due to oxidative stress caused by environmental factors or stress,” said Aaron. “The global market for antioxidants is growing at a considerable rate (at a CAGR of 4.71 percent over the period of 2013-2018) with rapid growth in the Asia-Pacific and North America markets (TechNavio, 2014). Some of this interest is due to the mainstream media covering the results of many clinical studies that show the beneficial effects of antioxidants.
“However, the field is confusing, as there is a broad array of antioxidants on the market, a lack of product differentiation and sometimes a lack of science behind products. Consumers, especially the affluent Baby Boomer market, seek good clinical evidence before purchasing a product. They are also looking for more specific solutions around health indications that matter most to them. For example, we know this consumer group is interested in antioxidants to help support skin health, cognition and joint health, and they are searching for the clinical evidence to back up the claims.”
Another hurdle, according to Dustin Williams, president, North America, Boundary Bend Wellness, is that there has been a gap in traceability and honesty in the antioxidant space the last several years. “Much like a lot of hot categories, antioxidants have been a victim of the typical ingredients markets with cheap deceptive products taking the share, as there are few better options,” he said. “It has also been somewhat slow with the evolution and advancement of products, as there hasn’t really been anyone taking the category to the next level—the biggest constraint being sourcing and material control. The growth possibilities are extremely positive when you look at all the various categories you can cross into utilizing antioxidants to boost the effectiveness of other ingredients.”
Research in the Field
According to Bornet, Horphag has dedicated many years of clinical research to ensure the safety and efficacy of its ingredients. The company’s ingredients are both standardized for quality control and patented.
He noted studies on Pycnogenol, a natural plant extract that originates from bark of maritime pine, and its antioxidant benefits, including:
• A new 2019 study shows that daily use of Pycnogenol in a topical patch can help improve osteoarthritis symptoms and reduce the need for NSAID (nonsteroidal anti-inflammatory drug) painkillers.
• A study in 2018 showed that Pycnogenol helps to reduce the symptoms of mild cognitive impairment associated with early onset dementia, including memory and ability to learn new things.
• A 2017 study published in [the] MDPI journal of Nutrients found that the polyphenols in Pycnogenol are directly distributed into joint synovial fluid to reduce C-Reactive Protein (CRP) levels and inhibit nuclear factor-kappa B to reduce inflammation at the source.
• Another 2017 peer-reviewed study demonstrated that Pycnogenol helps to alleviate the disruptive symptoms associated with menopause transition and reduce cardiovascular disease risk markers, C-Reactive Protein and Homocysteine.
• A study published in 2016 showed Pycnogenol’s benefits or curbing age-related muscle loss. The study showed significant improvement in muscular function and reduction of oxidative stress.
As for HP Ingredients’ MaquiBerry, it has proven success in combatting cholesterol levels and fighting inflammation, according to the company.
“ … MaquiBerry juice has been initially shown to have higher polyphenol content and scored higher for total free radical trapping potential and total antioxidant reactivity in antioxidant capacity tests, compared to different commercial berries,” Eng said. “In addition, maqui berry juice has been shown to be effective in inhibiting copper-induced LDL oxidation, suggesting it can support healthy cholesterol levels.”
Eng pointed to a 2011 study that has shown that MaquiBerry juice exhibited potent anti-inflammatory properties by inhibiting NFκB, a key regulator of inflammation response. It was also shown to reduce expression of COX-2, an enzyme responsible for inflammation and pain. A 2013 study showed that MaquiBerry’s delphinidin exerts immunostimulatory effects by activating NFAT [nuclear factor of activated T-cells] and inducing IL-2 and IFN-γ production through SOCE-mediated Ca2+ signaling.
One of Sabinsa’s ingredients, Curcumin C3 Complex, has demonstrated antioxidant effects, as proven by what many consider to be the “gold standard” of clinical trials.
“Many clinical studies have been conducted on natural antioxidants to support their health benefits. For example, studies on Sabinsa’s Curcumin C3 Complex, a standardized extract from turmeric (Curcuma longa), have suggested that its curcuminoids exert strong antioxidant effects against lipid peroxidation, hydroxyl and superoxide radicals, and improved activities of enzymatic antioxidants. In a randomized, double-blind, placebo-controlled trial, three-month supplementation of curcuminoids and piperine, in 118 diabetic patients, resulted in a significant increase in serum total antioxidant capacity and SOD activity (p<0.001, both), whereas serum MDA level was found to be significantly decreased (p<0.001) compared to the placebo group.”2
As innovations continue to develop, this also signifies that consumers are continuously seeking more information regarding safety and efficacy. FutureCeuticals has been able to show antioxidant results in humans with Spectra, a plant based, formula of fruits, vegetables and herbs that the website mentions has been shown to “inhibit free radical production, optimize cellular metabolic activity, and increase nitric oxide levels within the human body.”*
“Clinical human research is key to the increased consumer interest in antioxidants, thus of interest to the manufacturers/suppliers developing these new products,” Wheeler said. “Consumers want to know a product has been proven effective on humans—that there’s science behind the label claims, and that it is safe. They are reading product labels and making key buying decisions based on the facts. Manufacturers/suppliers know this and are looking for ways to differentiate their products from all the ‘me too’ products offering claims that lack science.
“ … Through our research at FutureCeuticals, it was clinically shown that Spectra, our flagship antioxidant product, inhibits these free radicals in humans, with a value-add of naturally boosting nitric oxide. Spectra has become a key component in many leading sports nutrition supplements. We were the ones that first were able to demonstrate and document real-time ROS [reactive oxygen species] scavenging occurring in humans. Before Spectra, it was only potential via ORAC calculations. Our scientist, working with a third-party laboratory, were able to develop a method that allowed the world, for the first time, the ability to demonstrate antioxidant action in human subjects.”
Trias, who noted that consumers seek out antioxidant products for a multitude of reasons, including to help with intense workouts, improve skin appearance, boost the immune system or to address chronic conditions.
“ … At American River Nutrition,” she said, “the research we are now mostly involved in examines DeltaGold’s (a tocotrienol ingredient derived from the annatto plant) effect on chronic ailments, primarily in a clinical setting. The fact that DeltaGold increased total antioxidant status in humans by more than 20 percent while at the same time decreasing lipids and inflammatory markers (including hsCRP) is only one finding.3,4 Based on research findings, we believe that DeltaGold’s supreme antioxidant capability also plays a role in improving bone turnover in post-menopausal women with osteopenia,5 and in reversing clinical markers of non-alcoholic fatty liver disease.6
“Supplement safety and bioavailability is also an important consideration for consumers of antioxidant products. For DeltaGold, an FDA GRAS [U.S. Food and Drug Administration, generally recognized as safe] ingredient, we have determined safety of daily dosages up to 600 mg in a 12-week clinical trial,7 while confirming bioavailability of various doses in human pharmacokinetic trials.”8,9
And according to Zelkha, it is important to also consider how many studies have shown positive beneficial results, along with the dates they were published. For black seed oil for instance, there have been more than 1,500 search results in the last year, but education around it has been minimal, so TriNutra is looking to help fill that void.
Overall, there’s been a shift in how antioxidants are being interpreted.
“More than 15 years ago, there was a boom in the research around antioxidants,” explained Johannes Haerle, PhD, senior technical manager, Evolva. “Mainly in-vitro studies were published, methods such as DPPH [2,2-diphenyl-1-picrylhydrazyl] and ORAC were commonly used to assess the antioxidant properties of a single compound. Later on, there were a considerable number of studies showing that these single compounds were first metabolized to several metabolites when administered to animals and humans. Therefore, the idea that a single compound could be the responsible for the antioxidant property was put into question. More recently, there is growing evidence that there is more likely a synergistic action due to the combination of compounds, which are more powerful than each single component (i.e. 1 + 1= 3).
“Finally,” he concluded, “the concept of an antioxidant property linked to only the counter-action of oxidative imbalance is not considered as the sole idea, as research has shown that antioxidant ingredients can act to directly scavenge free radicals or as secondary messengers by triggering cascades of reactions that could lead to anti-inflammatory properties as well, for example.” NIE
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
References:
1 United States Census Bureau. Older People Projected to Outnumber Children for First Time in U.S. History. 2018 6/19/2019]; Available from: www.census.gov/newsroom/press-releases/2018/cb18-41-population-projections.html.
2 Panahi et al. 2017.Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial. Inflammoph-armacology.25(1):25-31.
3 Qureshi, A.A., et al., Dose-dependent modulation of lipid parameters, cytokines, and RNA by delta-tocotrienol in hypercholesterolemic subjects restricted to AHA Step-1 diet. Brit J of Med & Med Res, 2015. 6(4): p. 351-366.
4 Qureshi, A.A., et al., Impact of delta-tocotrienol on inflammatory biomarkers and oxidative stress in hypercholesterolemic subjects. Clin. Exp. Cardiology, 2015. 6(4): p. 1000367.
5 Shen, C.L., et al., Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial. Osteoporos Int, 2018.
6 Pervez, M.A., et al., Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. Turk J Gastroenterol, 2018. 29(2): p. 170-176.
7 Shen, C.L., et al., A 12-week evaluation of annatto tocotrienol supplementation for postmenopausal women: safety, quality of life, body composition, physical activity, and nutrient intake. BMC Complement Altern Med, 2018. 18(1): p. 198.
8 Qureshi, A.A., et al., Pharmacokinetics and bioavailability of annatto delta-tocotrienol in healthy fed subjects. J Clin Exp Cardiolog, 2015. 6(11): p. 1000411.
9 Qureshi, A.A., et al., Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of Tocotrienols in Healthy Fed Humans. J Clin Exp Cardiolog, 2016. 7(4).
For More Information:
American River Nutrition, LLC, www.americanrivernutrition.com
Boundary Bend Wellness, www.boundarybendwellness.com
Evolva, www.evolva.com
FutureCeuticals, www.futureceuticals.com
Horphag Research, www.pycnogenol.com/home/
HP Ingredients, www.hpingredients.com
Sabinsa, www.sabinsa.com
TriNutra, www.trinutra.com, www.barringtonchem.com
