Back in August, the American Herbal Products Association (AHPA; Silver Spring, MD) made a significant announcement-that it had launched a Good Agricultural and Collection Practices (GACP) and Good Manufacturing Practices (GMP) assessment program for the botanical industry. 

This free, hands-on assessment program comprises checklists that those in the herbal industry-everyone from growers and harvesters to processors and manufacturers-can use when working in their area of the field to determine whether or not they are meeting what experts in those fields have defined as best practices. I recently spoke with Jane Wilson, AHPA’s director of program development, about how these standardized best practices tools can be used up and down the botanical supply chain, and about how they hopefully will help bolster quality control and transparency throughout the botanical industry.

First off, Wilson says, the increased public scrutiny around dietary supplements-and around the herbal supplement industry, in particular, as a result of 2015’s New York Attorney General (NY AG) investigation of herbal supplements and retailers-was the impetus that led AHPA to create the assessment tool. Wilson notes that, as a result of the NY AG investigation, many of the major supplement industry trade associations began undertaking self-regulatory initiatives. AHPA’s assessment tool, she says, is aligned with the association’s area of expertise, the botanical industry. “That was really the big driver, the recognition after the NY AG activity that there was more work that we could do as an industry to police ourselves and hold ourselves to high standards,” she says.

By 2006, she says, AHPA had already developed and released its Good Agricultural and Collection Practices for Botanical Materials document. But by mid-2016 (post NY AG), she said, AHPA decided to further update and translate those standards into actionable checklists for companies to use and make sure the checklists encapsulated new regulatory requirements such as those of the Food Safety Modernization Act.

The association gathered experts specializing in various areas of the botanical industry, and those experts helped to identify and develop the checklists. “We looked at things they were already using and got a sense of what it is that they do on a daily basis in terms of what would help their decision-making processes,” Wilson says. The result is nine separate checklists covering: 1) botanical identity and quality assessment, 2) cultivation, 3) wild collection, 4) general farm standards, 5) harvest, 6) post-harvest handling, 7) further processing, 8) food facility and farm facility, and 9) a dietary ingredient supplier assessment tool.

Wilson says these checklists can be used in a number of ways. First, those working in the field can use the individual checklists to self-assess their own procedures against expert-defined best practices as they do their work. But those operating farther upstream-for instance, those who purchase botanical ingredients-can also require their suppliers to utilize these checklists to confirm that the suppliers are adhering to best practices. “So, it can kind of be a push-pull,” Wilson says. “The suppliers can use it and provide it to somebody upstream who’s buying their botanicals, and they can say, ‘Hey, this is what we do, so you can see what our practices are.’ And then the people upstream can send it backward and tell a supplier, ‘Well, we want to buy your material, but we’d like you to fill this out so that we can get a sense of what your practices are around certain activities and how you produce your botanical material.’” Wilson also points out that the checklists are editable Word docs so that companies can change any portions that they feel don’t apply to their business, etc. “They’re intended to be flexible so that companies can use them to the best advantage,” she says.

If anything, Wilson says, the hope is that these tools will emphasize the need for documentation. Because, she says, “I think the question goes to, ‘Are you doing it, and are you 

 it?’” Because those can be two different things. So, when somebody starts asking you to 

whether you’re doing something, it’s helpful if you have an SOP that you can show them that says this is what our staff is supposed to do, etc.”

“There are probably segments of the botanical industry where a lot of these practices are just generally recognized, but it’s not anything that anyone’s thought, ‘Well, I need to keep a record of the fact that I’m doing that,’ or ‘I need to be able to demonstrate that somebody has been adequately trained on that,’” she continues. “So, it’s just formalizing, hopefully, a lot of these activities that have been well-recognized for a long time, but now, because of some of these issues, like attention from the NY AG, that it becomes important to be able to document specifically that you are doing these things and that you’ve been adequately trained to do these things.” 

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I recently spoke with Jane Wilson, AHPA’s director of program development, about how its standardized best practices tools can be used up and down the botanical supply chain, and about how they hopefully will help bolster quality control and transparency throughout the botanical industry.

Bolstering Botanical Best Practices 

The cereal bars market is maturing after years of strong growth, particularly in the United States, which is the largest market in the world. Global and U.S. launches of cereal and energy bars recorded by Innova Market Insights fell slightly in the 12 months to the end of June 2017, although numbers were still well above totals for the previous five years. The mature U.S. market saw just over a 50% rise in launch numbers over the previous five-year period (June 2012–2017). Meanwhile, the less well-developed regions of the world saw even more dynamic growth with a surge of more than 90% globally over the same period.

As interest in cereal bars has grown, the category has broadened to encompass a wide range of products, including granola/muesli, breakfast, nutrition, and energy and performance bars. With increased competition in this market, however, many product makers seek to highlight points of differentiation by combining features and blurring definitions, often carrying a range of ingredients and product claims designed to appeal to the widest possible audience seeking nutritious, tasty, and portable snacks in a highly competitive environment.

Market Differentiation: What’s In and What’s Out


The nutrition bars sub-category focuses specifically on health, but most products launched in the cereal bar market also use health claims. More than 83% of global launches recorded by Innova Market Insights in the 12 months to the end of June 2017 used at least one kind of health positioning; in the United States, nearly 95% of cereal bars launched in the same period had some kind of health positioning.

Whole-food nutrition and natural ingredients are key areas of interest, with clean labeling and “free from” continuing to be areas of focus. Nearly half of U.S. launches featured one or more claims relating to naturalness, no additives/preservatives, or organic certification. This figure rises to nearly two-thirds when GMO-free claims are also included. The growing use of GMO-free positionings has been apparent in the global food and drinks market in recent years, but has been especially prevalent in the United States and for cereals. Innova Market Insights estimates that 48% of newly launched products use this type of claim, up from around 10% five years previously.

Cereal bar launches with “free-from” positionings are not far behind clean labelling in the United States, with 64% featuring allergen-free, gluten-free, lactose-free, vegan, and vegetarian claims. Gluten-free is the leading health positioning for cereal bars as a whole. This positioning is used for more than 60% of all new product introductions.

Other key areas of interest include the use of whole grains, fiber, and, more recently, protein. Protein is now the most significant of the three, with “high/source of protein” claims used for 47% of launches in the 12 months to the end of June 2017, compared with 34% for fiber and 17% for whole grains.


Interest in whole grains has been key to the growth of the cereal bars market for many years, but more specific types of grains are increasingly being featured. For instance, ancient grains and seeds have seen rising levels of new product activity in the food and drinks market over the past few years, with their reappearance in modern diets reflecting increased interest in products such as quinoa, chia, millet, buckwheat, sorghum, spelt, amaranth, teff, and kamut. Such grains and seeds are being positioned as traditional, natural, and nutritious. Cereals, perhaps not surprisingly, have seen especially high levels of activity, with nearly one-fifth of launches featuring ancient grains, rising to nearly 24% for cereal and energy bars. 

Some launches profile the inclusion of ancient grains very specifically, with recent introductions including Thrive Ancient Seeds Superfood Nut Bars from GoMacro (Viola, WI) and Ancient Grains Triple Berry Nut Crispy Bar from Pure Organic (Solana Beach, CA). The latter product features an organic ancient grains blend of quinoa, brown rice, amaranth, flaxseed, and hemp seed. 

Another on-trend ingredient popular in the cereal bars category is hemp, with the United States again leading developments. Its success is attributed to several factors; in addition to being a source of high-quality plant-based protein, it is also high in polyunsaturated fatty acids, rich in B vitamins and minerals, and contains high levels of both soluble and insoluble dietary fiber. 

More than one-quarter of U.S. food and drinks launches featuring hemp in the 12 months to June 2017 were cereals, with cereal bars alone accounting for more than 21%. Recent launches with a strong focus on hemp include Everbar Hemp Powered Bar from Livity Foods LLC (Rockville, MD) and the Evo Hemp Organic Raw from Hemp Healthy (Boulder, CO). The Evo bars also focus on other key trends, being organic, raw and cold-pressed.

Taste, Convenience, and Novelty Remain King


While health and nutrition concerns appear to be driving product development, it must not be forgotten that taste, convenience, and novelty are also very important if the products are to compete successfully with other snacks and meal replacements. Increasingly indulgent ingredient blends and flavors are also featuring strongly, including more savory options and sweet–savory combos, along with the development of new formats such as miniature and bite-size options in resealable pouches or sharing bags.

Interest in portable, tasty nutrition reaches new heights.

Setting the Cereal Bar High

When it comes to natural colors, consumers have spoken loud and clear: gone are the days of indifference about artificial colors and preservatives. Tammi Higgins, business unit head, colors, Lycored (Orange, NJ), points to recent Nielsen data indicating that more than three in five consumers globally say they do their best to avoid artificial colors. She notes that when Lycored conducted a 506-person survey to determine whether consumers would be willing to pay more for products featuring natural colors and flavors, nearly nine in 10 said that they would. And while it’s clear that natural colors are in, it can still be difficult for formulators to find stable, natural color solutions, namely because of the challenges natural colors face.

For one thing, natural colors are often more expensive to formulate with than their artificial counterparts. The main challenge, however, is creating a natural color that holds up when exposed to particular rigors of the manufacturing process. Light exposure, heat sensitivity, and interactions with other ingredients are key challenges natural color companies face-obstacles that are largely avoided when working with synthetic ingredients. “The synthetic food colorants that the food industry came to rely on over the past 50–60 years are relatively very well-behaved and consistent in their performance,” Winston Boyd, director of technical services, Gold Coast Ingredients (Commerce, CA), tells 

. “Natural colorants, on the other hand, may have issues with pH, heat, and light stability.”

In addition, it’s critical that manufacturers understand a natural color’s behavior can be “highly dependent on the application,” Boyd states.

The behavior of certain color ingredients, for instance, may be affected by other ingredients within the same food or beverage formulation. “For example,” says Campbell Barnum, vice president, branding and marketing, D.D. Williamson (DDW; Louisville, KY), “vitamin C will enhance the stability of finished beverage products colored with carotenoids like beta-carotene and paprika oleoresin, but the same vitamin will cause the degradation of anthocyanins.”

Even once a natural color is successfully formulated, however, keeping the color of a finished product vibrant once it hits the market can be just as tricky.

To ensure the stability of its natural colors, DDW, Gold Coast, and Lycored are focusing on testing and research. “DDW has standard methods to test parameters that influence the stability of colors,” Barnum says. “We use instrumentation to measure color before and after product application stress testing in heat, light, or different pH environments. For example, we will store food products with colors for eight weeks at elevated temperature. The heat test allows DDW to approximate the shelf life of colors in finished products.” Barnum says DDW’s NaturBrown ingredients, for instance, are formulated from 100% natural sources and “have the optimal balance between stability, flavor, and color.”

Lycored has focused its innovation in the natural colors category on bright, bold reds, yellows, and oranges, including its lycopene-based Tomat-O-Red colorant, which is formulated from the carotenoid extracted from tomatoes and is highly heat, light, and pH stable. But even these colors can face challenges at times, the company says, which is why it continues to embark on extreme stability testing to improve performance.

Gold Coast, meanwhile, says it is “working daily to develop specific color formulations to meet the demanding challenges of our customer base.” Boyd says that Gold Coast currently has some “entirely new concepts” in the pipeline aimed at solving some of the challenges associated with working with natural colorants.

Ultimately, one of the best ways for color manufacturers to ensure natural color stability is identifying the right colorant. Both Higgins and Boyd stress the importance of selecting a colorant that you know is going to give you stability. “It’s much better doing that than adding chemicals to prevent bleeding, or changing your manufacturing processes,” Higgins says.

Boyd agrees: “A knowledgeable color technologist can steer the product developer to the right class [or] formulation of natural food colorant for the application. If we understand the challenges earlier in the process, it gives us much more flexibility in achieving the desired result.”

If companies want to get in on the natural trend, there’s certainly work to be done-but they won’t be starting from scratch, thanks to supplier advancements. Given the manufacturing challenges and costs associated with achieving convincing, highly stable natural colors, is it worth it? Naturally.

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Natural Color Stability: Challenges and Opportunities

Brain health supplements are a growing market segment thanks to several recent research developments and the rise of age-related cognitive decline. One market report by Research and Markets states that the global brain health supplement market was worth $2.3 billion (USD) in 2015, and worldwide sales of brain health supplements are projected to exceed $11 billion (USD) by 2024.

This report points to an aging population of highly educated professionals as the driving force behind the growth in demand. In addition, increased awareness about the benefits of supplements for supporting concentration and memory among college students, scientists, and entrepreneurs has increased sales in this category, according to the firm.

Research and Markets also states that the largest sales channel for brain health products is online stores, which are outpacing drug stores and supermarkets in sales growth due to more variety in price points, more product launches, and a greater availability of private labels.

As demand for brain health ingredients grows, so does interest in research that demonstrates the value of new and established nutrients for promoting healthy brain function. New studies continue to demonstrate the specialized beneficial effects of various compounds on the brain, particularly for memory and cognition support.

While there are too many brain health ingredients on the market to examine them all in one sitting, what follows is a shortlist of some popular ingredients with new studies that demonstrate their benefits. (Note that this list is by no means exhaustive, and is intended to be a sampling of some compelling recent studies.)

Omega-3 fatty acids, the class of polyunsaturated fatty acids typically used as metabolic regulators in dietary supplements, are also useful in cognitive supplement formulations.

Gretchen Vannice, RDN, head of Global Nutrition Education at Organic Technologies, the parent company of AlaskOmega (Coshocton, OH), says omega-3 fatty acids are essential to healthy brain function, and that supplements are an ideal delivery form given that most Americans do not consume enough omega-3 fatty acids in their diet.

Says Vannice, “90% of the omega-3 fats in the brain are DHA. In the adult brain, DHA is especially concentrated in gray matter and is enriched in brain cell membranes, where it directly influences functional processes like membrane fluidity, gene expression, myelination, neuroinflammation, neurotransmitter release, and more.”

Vannice says that decades of research have demonstrated that high levels of omega-3 fatty acids are associated with better cognition, slower cognitive decline in older adults, improvements in episodic memory in women, and improvements in working memory in men.

Perhaps the most promising new brain health application of omega-3s is assisting athletes in recovering from traumatic brain injuries (TBIs). One randomized, double-blind, placebo-controlled clinical trial on DHA omega-3 fatty acid supplements followed 81 National Collegiate Athletic Association Division I football players for 189 days, the entire duration of the college football season. Participants were given 0, 2, 4, or 6 grams of DHA per day. The study tracked measures of mild traumatic brain injury, including changes in serum neurofilament light (NFL), which is a biomarker of axonal injury. Elevated serum NFL levels is a telltale sign of mild traumatic brain injury and is common among football players.

This study found that supplementing with DHA attenuated axonal injury, particularly among starting players, who tend to have more playing time and physical contact, and are therefore more likely to suffer brain injuries.

“This was the first study to examine prophylactic use of omega-3 supplements in football players,” Vannice notes. “While the study used DHA only, based on the literature, I can predict that equal or higher amounts of EPA would provide additional benefits not only for brain health, but also for physical health and recovery.”

Extending the Shelf Life of Phospholipid Supplements

Phospholipids are naturally occurring lipids present in all cell membranes that contain at least one phosphate group. Phosphatidylserine (PS) is a type of phospholipid that signals phagocytes to begin apoptosis.

Soft Gel Technologies, Inc. (Commerce, CA) President and CEO Steve Holtby says PS is an essential building block that works to stabilize the membranes of brain cells, thereby protecting brain cell activity and limiting cell deterioration. He also notes the ingredient’s role in stimulating memory and cognition as well as regulating mood.

Says Holtby: “PS supplements have been demonstrated in clinical trials to improve memory, concentration, word recall, and mood in middle-aged and elderly subjects. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists.”

Holtby says that early PS ingredients were extracted from the brains of cows, which presented potential dangers concerning the transfer of infectious diseases such as bovine spongiform encephalopathy. To resolve this risk, manufacturers like Soft Gel Technologies developed a means of extracting PS from soybeans and other plant sources.

However, delivery mechanism optimization presented further challenges. PS tends to degrade when stored in a soft gel, which makes it difficult to produce a PS supplement that appeals to older supplement users who have readily embraced soft gels as a delivery mechanism.

“To overcome this problem,” Holtby explains, “we created a fluid dispersion PS material that has a greater stability. We’ve conducted stability and shelf-life studies, and we’ve found that the soft gel capsules maintain ingredient quality and level for a long period of time. Shelf-life studies performed by an independent laboratory for phospholipid analysis found that even after 24 months, the material showed absolutely no degradation.”

Citicoline May Hold Promise for Schizophrenia Patients

A naturally occurring cholinergic compound, citicoline promotes normal brain function and supports neuroprotective mechanisms by stimulating the production of phosphatidylcholine and acetylcholine in the brain.

Clinical trials have examined citicoline as a therapy for addressing substance dependence, bipolar disorder, and traumatic brain injuries. Research is expanding into its benefits for schizophrenia patients.

One randomized, placebo-controlled trial followed 43 adult schizophrenia patients for 16 weeks.

 Before the trial, participants were assessed using the PANSS scale, which measures schizophrenia symptom severity. Individuals were assigned a score correlated to the sum of their ratings for five symptoms on the PANSS negative-symptom subscale. Participants in the experimental group received gradually increasing doses of citicoline, starting at 500 mg/day on the first day of the trial and ending with 2,000 mg/day by the beginning of the second week.

Over the course of the 16 weeks, both the placebo group (n=19) and the experimental groups (n=15) gradually lowered their PANSS scores. However, the experimental group scores decreased by one full standard deviation, whereas the placebo group scores decreased by only one half of a standard deviation.

While a follow-up double-blind clinical trial failed to replicate a statistically significant reduction in the experimental group’s PANSS scores, it did find that citicoline had a significant effect on global functioning scores and free verbal recall.

These studies are significant in that they found a therapeutic effect of citicoline on schizophrenia symptoms. Schizophrenia is a challenging condition to address. The negative symptoms of the disease in particular, such as apathy and avolition, are notoriously resistant to conventional therapies, partly because schizophrenia medications like haloperidol and risperidone tend to induce these symptoms in healthy individuals.

The fact that the first study found a reduction in PANSS scores indicates that citicoline may hold promise in addressing the negative symptoms of schizophrenia.  The study authors caution, however, “further study…is warranted in larger studies that will have greater (statistical) power.” 

Arginine Boosts Focus, Mental Acuity, and Problem-Solving Speed

Arginine is a well-studied amino acid frequently used in athletic and heart health supplements, but now, a silicon-bonded arginine variant is showing promise for cognitive applications. Double-blind, placebo-controlled human clinical trials have now found that arginine silicate is effective at improving mental acuity, cognitive function, and subjective feelings of mental energy.

Jim Komorowski, chief science officer at Nutrition 21 (Purchase, NY), says a small daily dose of his firm’s branded and patented arginine silicate complex Nitrosigine resulted in significant increases in feelings of energy in two clinical trials involving healthy participants.

Both studies were double-blind, placebo-controlled crossover trials involving healthy subjects (n=16 and n=11, respectively). Experimental groups received 1.5 grams of Nitrosigine per day. Relative to the placebo groups, the experimental groups reported feelings of higher energy and performed better on cognitive tests.

Says Komorowski, “Nitrosigine supplementation also improved response time on a test of cognitive function, and after a single dose, Nitrosigine has been clinically shown to increase mental acuity and focus by 33% within 15 minutes. The impact on mental acuity also continues to build over time...Although studies on other nutrients may have reported some effects on brain function, those effects took weeks or months to develop.”

Resveratrol Supports Memory in Healthy Individuals and Those with Cognitive Decline

A naturally occurring polyphenol commonly found in grapes and berries, resveratrol is most well known as an anti-aging ingredient. Gene Adamski, national sales manager at Evolva (Reinach, Switzerland), and his colleagues Angela Tsetsis and Ernesto Simon say that resveratrol protects grapes from harsh environmental conditions, and that the compound has a similar effect in humans by promoting healthy aging at a cellular level.

Evolva’s team says that resveratrol supports a balanced inflammation response in the brain and improves cerebral blood flow, which results in mood and cognition benefits.

Recent human studies indicate that regular resveratrol intake can support brain function in both patients with Alzheimer’s disease and normal, healthy individuals. One randomized, double-blind, placebo-controlled trial gave varying doses (500 mg/day to 2 grams/day) of resveratrol to 119 patients with Alzheimer’s disease for 52 weeks. This clinical trial found that relative to a placebo, resveratrol resulted in an improvement in Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale scores, changed AD biomarker trajectories, modulated neuroinflammation, and induced adaptive immunity.

A second randomized clinical trial found that 75 mg of resveratrol given twice per day for 14 weeks improved performance on verbal learning and semantic memory tasks and boosted blood flow in the brains of 80 healthy postmenopausal women.

The Evolva team says that these studies showcase the mood-boosting and cognitive-enhancing properties of resveratrol and also serve as a jumping-off point for investigations into resveratrol’s long-term health effects: “The same research group is conducting a bigger follow-up study where they investigate the effects of Veri-te resveratrol in cerebrovascular function, cognitive performance, and bone health.”

Blueberry Extract Supports Episodic Memory in Older Adults

) is a polyphenol-rich supplement that supports healthy blood pressure levels. In addition, Dan Souza, nutrition and health category manager for the branded blueberry product ThinkBlue by Naturex (Avignon, France), says wild blueberry extract has been clinically shown to improve episodic memory in senior citizens.

One randomized, double-blind, placebo-controlled human trial on the effects of ThinkBlue-branded blueberry extract involved 120 healthy participants between 65 and 80 years of age. This six-month study followed a group of seniors who consumed 111 mg of ThinkBlue per day.

After three months, Souza says, participants in the experimental group saw a 7% improvement in episodic memory. After six months, participants saw a six-point drop in systolic blood pressure. This study is slated for publication at the end of 2017.

Souza says that these findings are significant because they demonstrate a clear opportunity to resolve an ongoing challenge that seniors face: the degradation of episodic memory.

He states, “Episodic memory, the memory of personally experienced events, shows the greatest degree of age-related decline. There’s robust and growing literature illustrating the cognitive health benefits of wild blueberries, but until now, there hasn’t been a compliance-friendly, clinically substantiated dose of wild blueberry for nutritional supplement applications.”

Souza also notes that past studies were conducted using much higher doses (at least 10 grams per day), whereas the ThinkBlue study showed a statistically significant improvement in episodic memory with a much smaller dose of just 111 mg per day.

The evidence also suggests that blueberry supplementation can improve verbal learning skills, and that the ingredient’s effects on memory apply both to short- and long-term memory.

CÃ©cile FrÃ©mont, the communications manager for Activ’Inside (Libourne, France), says blueberry’s high concentration of polyphenols, anthocynanins, flavonols, and phenolic acids make it an ideal brain supplement, particularly for older adults with memory issues.

In one randomized, double-blind, placebo-controlled clinical trial, 215 healthy adults between the ages of 60 and 70 received 300 mg of Activ’Inside’s branded Memophenol grape/blueberry extract or a matching placebo twice per day for six months. According to FrÃ©mont, participants were assessed on the Verbal Recall Memory (VRM) test and the Paired Associates Learning (PAL) test, which evaluate short-term working memory and long-term episodic memory, respectively.

Relative to the placebo group, subjects who received Memophenol recalled 60% more words on the VRM test and had significantly fewer errors on the PAL test. Study authors concluded that Memophenol supplementation reversed eight years of cognitive degradation, FrÃ©mont explains.

FrÃ©mont says this and other studies show that some brain health ingredients are more effective when formulated in blends: “Ten studies have been performed with a scientific R&D approach using this same framework, and they’ve revealed that grape and blueberry compounds are better absorbed when consumed in a specific ratio that boosts the cognitive properties of each single ingredient.”

Botanical brain health supplements, whether single-ingredient products or blends, have a variety of beneficial effects on the brain.

Deanne Dolnick, science director at TR Nutritionals (Alpharetta, GA), says botanical products like Gingko biloba extract and Bacopa monnieri extract are among the most popular brain health botanicals on the market, and for good reason.

“Ginkgo biloba extract has been the gold standard in brain health botanicals for a very long time,” says Dolnick. “It’s still popular for supporting memory and cognitive function, as well as increasing blood flow and reducing inflammation.”

Dolnick says bacopa is also an important brain health supplement due to its ability to repair damaged neurons and restore degraded synaptic activity.

Until a few years ago, it was unknown whether the dendrites of neurons could repair themselves.

 Now, researchers have confirmed through animal studies that bacopa induces dendritic proliferation and promotes neuron communication.

Bacopa also has anti-inflammatory properties that may have applications for a variety of central nervous system disorders, as demonstrated in a recent in vitro study involving microglial cells grown from mice.

This study examined the effects of bacopa infusions, teas, and alkaloid extracts (made from 10 grams of powdered bacopa extract) on cell cultures, specifically the neurotoxic M1 microglia and the neuroprotective M2 microglia. After administration, the infusion and a high-concentration alkaloid extract significantly inhibited the release of TNF-alpha and had an anti-inflammatory effect.

Dolnick says this study is significant because it demonstrates that Bacopa monnieri “inhibits the release of inflammatory cytokines from microglial cells and inhibits enzymes associated with inflammation in the brain.”

Spearmint a Popular Brain Supplement for Athletes

) has been shown to support memory, attention, planning, and reasoning when administered in high doses.

Kim Colletti, global cognition product manager for Kemin (Des Moines, IA), says spearmint strains bred to be high in polyphenols have beneficial effects on focus as well as working memory, which processes new stimuli and uses recent memories to solve problems. Colletti says polyphenols like those in spearmint have been found in studies to reduce oxidative stress, boost acetylcholine levels, promote neurogenesis, and have neuroprotective properties.

Colletti points to a recent randomized, double-blind, placebo-controlled clinical trial on Kemin’s branded spearmint supplement Neumentix Phenolic Complex that involved 142 healthy, active men and women in their late 20s. The experimental group received a daily 900-mg dose of Neumentix, and participants were assessed using computerized cognitive test batteries after 0, 7, 30, and 90 days.

Says Colletti, “The participants taking Neumentix had significantly higher scores in sustained attention after 30 days of supplementation, and these improvements were still present after 90 days. These findings build on earlier work and further emphasize the uniqueness of this special ingredient.”

Ashwagandha Reduces Mental Stress and Enhances Neurotransmitter Effects in Studies

) is an adaptogenic herb commonly used in Ayurvedic medicine.

Bruce Abedon, PhD, vice president of scientific and regulatory affairs for NutraGenesis (Brattleboro, VT), says ashwagandha also supports normal memory function and cognition in addition to reducing cortisol levels in human clinical trials.

Abedon says that the glycowithanolide bioactives present in ashwagandha can also inhibit the enzymes that break down neurotransmitters, thereby extending the duration of neurotransmitter effects.

“For example, ashwagandha helps to inhibit acetylcholinesterase, an enzyme that breaks down acetylcholine. Acetylcholine is active in the hippocampus, which is associated with memory and learning. So, reduced degradation of acetylcholine can produce cognitive benefits (by enhancing memory and learning).”

One double-blind, placebo-controlled crossover human clinical trial followed 20 healthy subjects for 43 days. Subjects took 250 mg of NutraGenesis’ branded ashwagandha product Sensoril twice per day for 14 days, and were evaluated on cognitive function tests of reaction time, digital system substitution, digit vigilance tasks, and card sorting tests on day 15. After a 14-day washout period, the subjects crossed over to the opposite group for another 14 days.

Subjects taking the ashwagandha supplement scored significantly higher on measures of psychomotor performance, working memory, reaction time, and information processing ability compared to the placebo group.

Abedon says that this study demonstrates the effectiveness of ashwagandha as a cognitive supplement: “This study shows that Sensoril is effective at multiple doses, in multiple populations, when assessed both subjectively and objectively using validated test measures.”

According to Abedon, NutraGenesis’s branded and patented ashwagandha product Sensoril differs from traditional ashwagandha in that it has standardized to contain over 10% glycowithanolides, whereas the concentration of this component in traditionally prepared ashwagandha can vary.

Curcumin Clears Amyloid Plaque and Neutralized Free Radicals

A linear diarylheptanoid extracted from the dried rhizomes of the 

plant, curcumin is often used as a brain health supplement for its mood-stabilizing and stress-reducing properties. Now, research suggests that curcumin may play an important role in supporting a balanced immune response and clearing amyloid plaque in the brain.

In a recent double-blind randomized crossover clinical trial, 30 obese participants (BMI >30) with varying degrees of comorbid anxiety and depression received 1 gram of curcumin per day (or a corresponding placebo) for 30 days. After a two-week washout period, subjects crossed over to the alternate condition for an additional 30 days.

Participants were assessed on their anxiety and depression using the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory at 0, 4, 6, and 10 weeks.

The study found that curcumin supplementation was associated with a statistically significant (p<0.05) reduction in mean BAI scores relative to a placebo.

Shaheen Majeed, president of Sabinsa Worldwide (East Windsor, NJ), says this and other studies demonstrate the impressive brain health benefits of curcumin: “Several recent studies have demonstrated that curcumin can help restore equilibrium by improving mood, regulating stress and anxiety, and protecting the brain against aging and neurodegenerative diseases like Alzheimer’s.”

Lutein Benefits Memory and Academic Performance in Children

A naturally occurring terpenoid, lutein is commonly used as a supplement for the eye and skin health markets. As a brain health supplement, lutein is typically used to prevent age-related cognitive decline.

Kemin’s Global Manager of Vision Products Ceci Snyder says lutein is the predominant carotenoid in the brains of children and older adults.

“In children, lutein makes up more than half of the brain’s total carotenoids, which indicates that lutein plays a role in brain development. Higher brain levels of lutein are also related to better cognitive function in older adults.”

Snyder speaks of one recent clinical trial involving 40 children between ages seven and 10. In this randomized, parallel-design clinical trial, participants were assessed for aerobic fitness via a modified Balke treadmill protocol and completed a task to measure relational memory performance. Participants were also assessed for macular pigment optical density (MPOD) and adiposity.

The study found that higher levels of aerobic fitness and MPOD were correlated with fewer memory errors, and that MPOD accounted for a significant amount of the variance in memory performance.

Snyder says this study is important because it demonstrates the importance of lutein throughout life. She states, “Lutein appears to help maintain brain health and function by protecting the brain from oxidative stress and inflammation.”

OmniActive (Morristown, NJ) Vice President of Global Marketing Lynda Doyle says lutein is also a potent antioxidant that boosts academic performance and prevents age-related cognitive decline. While the exact mechanism of action remains unclear, Doyle says the current rationale is that lutein has anti-inflammatory and antioxidant properties.

One double-blind, placebo-controlled clinical trial on 59 healthy subjects between 18 and 25 years of age measured the effects of carotenoid supplementation on a variety of markers such as antioxidant concentration, inflammation, and brain-derived neurotrophic factor (BDNF), a neurotrophin associated with learning, memory, and higher cognitive processes.

This study found that relative to the placebo group, lutein supplementation significantly improved antioxidant and BDNF levels, and significantly decreased inflammation markers. 

The latest research on brain health ingredients indicates products are meeting consumer needs and offer significant opportunity for category growth.

Smart Ingredients for Brain Health

In the nutritional-supplements industry, ingredient fads come and go, waxing and waning in popularity and media attention. Some ingredients, however, earn the respect of consumers, physicians, journalists, and scientists alike, and retain their good reputation indefinitely. Coenzyme Q10 (CoQ10) is one such ingredient. 

Discovered in 1957 and finding a solid foothold in the supplements market within the last 15–20 years, CoQ10 “is one of the most studied-and more importantly, understood-dietary supplements” on the market today, says Scott Steinford, executive director at large of the CoQ10 Association (Salt Lake City, UT).

He explains that the human body synthesizes CoQ10, but our production of this fat-soluble compound declines as we age. “CoQ10 is utilized by every cell of the human body and is an intricate contributor to the ATP process,” Steinford continues. “In simplest terms, CoQ10 is responsible for converting food into energy. The effects of CoQ10 deficiency are most noticed in the organs that require the most energy production.” These organs include the liver, kidneys, and, of course, the heart.

“Thousands of studies have demonstrated the activity and importance of CoQ10 in heart health and many other human and veterinary health aspects,” Steinford contends, and demand for the ingredient seems to be in line with that assertion. “A 2017 ConsumerLab.com survey of more than 9,500 respondents listed CoQ10 as the third most popular dietary supplement behind vitamin D and fish oil,” Steinford points out.

What’s more, some research has suggested that this ingredient holds promise for other emerging areas such as oral health. “The pharmacology of coenzyme Q10 indicates that it may be an agent for treatment of periodontitis,” say Shobra Prakash and co-researchers in the 

, and “coenzyme Q10 may possibly be effective as a topical and/or systemic role or adjunctive treatment for periodontitis either as a stand-alone biological or in combination with other synergistic antioxidants (i.e., vitamins C and E).”

As such, “we are seeing strong sales growth in the natural channel in toothpaste with CoQ10 as an active ingredient,” says Jamie Phillips, director of scientific affairs at SPINS (Chicago, IL). While sales are relatively small, SPINS natural products specialist Kimberly Kawa states, “Sales in the Oral Care category within the Body Care department are up about 7%,” with Nature’s Answer’s PerioBrite toothpaste (a brightening formula with CoQ10 and folic acid) leading the way.

In the Vitamin, Mineral, and Supplements category only, total sales of CoQ10 for the 52 weeks ending August 13, 2017 were roughly $164 million, down slightly (about 2%) from the previous year, while sales of ubiquinol (i.e., the fully reduced form of CoQ10) were up 1.3% from the previous year, according to the most recent SPINS data available. The slight downward trend of conventional CoQ10 (i.e., ubiquinone), says SPINS’ Phillips, is likely due to the fact that “it is an established supplement” with “no new news or marketing messages” in recent months.

As for ubiquinol, “it is more expensive than [ubiquinone], but has been found to be more effective for persons with certain conditions that inhibit the necessary conversion of CoQ10 in the body,” Kawa notes.

CoQ10 Association’s Steinford adds that ubiquinol is gaining popularity with consumers who are concerned with absorption and bioavailability; however, “ubiquinone [CoQ10’s fully oxidized form] still commands 90% of the overall CoQ10 market and remains the most recommended form of CoQ10,” he says.

Among physicians, CoQ10 has earned trust and confidence, too. A CoQ10 Association study of 100 cardiologists found that CoQ10 was the most-recommended supplement among this group and that 71% of cardiologists recommend the ingredient to “at least some” of their patients.

Demand for CoQ10 is on the rise. “In 2000,” Steinford says, “the global demand for CoQ10 was 37 metric tons, while in 2016, the global demand for CoQ10 exceeded 750 metric tons.” One reason for this significant uptick, he explains, is that the typical dosage increased from 5 to 30 mg in 2000 to about 120 mg today. He adds that the even higher 200-mg CoQ10 dosage is the fastest-growing one.

Vincent Tricarico, vice president of contract manufacturing at NutraScience Labs (Farmingdale, NY), says he is noticing CoQ10 in a “growing variety of formulations” beyond those for traditional cardiovascular support, including vision-support and antioxidant-specific formulations.

As for delivery systems, Tricarico says an oil-based liquid contained in either softgels or “standard two-piece veggie or gelatin capsules” is best. Steve Holtby, president and CEO of Soft Gel Technologies (Commerce, CA), agrees, specifying that fat-soluble CoQ10 is absorbed more readily when “placed in lipid media such as softgels or when taken with foods containing fat. A softgel delivery system plays a key role in enhancing the effectiveness of CoQ10 getting into the bloodstream,” he says.

“CoQ10, being a highly lipophilic and crystalline material, presents specific challenges that require an innovative approach,” Holtby continues. “Absorption [by the body] is dependent on the number and size of CoQ10 crystals within the product.” (The fewer and smaller the crystals, the better.)

He describes how Soft Gel Technologies’ CoQsol-CF formulation dissolves CoQ10 in solution, resulting in a “completely solubilized CoQ10 that does not require heat or synthetic solvents,” and the mixture “fully resists recrystallization at ambient temperature ranges.” By improving dissolution, he asserts, absorption is enhanced.

For those looking to break into the heart-health supplement space, combining CoQ10 with omega-3 fatty acids “can serve as a great starting point” for a heart-health formulation, says NutraScience Lab’s Tricarico.

The CoQ10 Association’s Steinford agrees, citing a July 2017 study investigating the effect of a CoQ10 and omega-3 fatty acid combination on statin therapy in some heart patients, in which the researchers reached the conclusion that “the results of this pilot study suggest the possible beneficial effects of triple combination [statins, omega-3s, CoQ10] on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.”

Tricario adds: “Viewing omega-3 fatty acids and CoQ10 independently, there is ample evidence to suggest the combination of the two ingredients will collectively work to improve heart health.”

CoQ10 supplementation is commonly recommended by physicians as an adjunct to statin therapy; the fact that CoQ10 levels in the body are reduced when a patient takes statin medication is widely known. “Given that it’s also common to take an omega-3 supplement with a statin,” says Harry Rice, PhD, vice president of regulatory and scientific affairs at the Global Organization for EPA and DHA Omega-3 (GOED; Salt Lake City, UT), “then an omega-3 and CoQ10 combination product makes perfect sense.”

One such product is Fish Oil Q from Carlson Labs (Arlington Heights, IL), launched in 2007. “Carlson was the first company to introduce an oil-based CoQ10 way back in the 1980s,” says nutritionist and educator Jolie Root of Carlson Labs, “so it was a natural progression to combine omega-3s and CoQ10 in one formula.” She echoes GOED’s Rice, stating, “Since fish oils are routinely prescribed as secondary prevention of heart events in persons with known heart disease, who are also likely to be taking statins, the combination just makes perfect sense.”

Nordic Naturals (Watsonville, CA) also offers combination omega-3–CoQ10 products, including its Ultimate Omega+CoQ10 softgels, which contain fish oil and the ubiquinone form of CoQ10; and its Omega LDL, which is formulated with concentrated omega-3 fish oil, ubiquinone, and red yeast rice.

Nordic Naturals is now also offering a ubiquinol softgel containing 100 mg of a ubiquinol ingredient from Kaneka Nutrients (Pasadena, TX) in extra-virgin olive oil. “We expect to see ubiquinol implemented in many more formulations, including with omega-3s, for consumers among the baby-boomer generation,” says Kaneka North America’s product-development manager Sid Shastri.

“In many ways, ubiquinol and omega-3s are ideal partners in the battle for cardiovascular health. While ubiquinol is a potent lipid antioxidant that is active in the production of cellular energy necessary for the heart and other energy-intensive organs to function efficiently, omega-3s are valued for their impact on reduction of blood lipids, particularly triglycerides as well as blood-platelet functionality and vasodilation,” he states. “By reducing blood lipids and protecting against oxidation of lipids (which then penetrate into vascular arterial intima-an important initiation point in the pathophysiology behind atherosclerosis), there is ample rationale for the combination of these two cardio-protective nutrients.”

While ubiquinone reigns supreme among CoQ10 sales, interest in ubiquinol is building. Shastri of Kaneka North America, notes that “as consumers over 40 years of age become more educated about ubiquinol, as opposed to conventional CoQ10, they have come to appreciate the value of ubiquinol in the production of cellular energy as they age.” 

He adds, “The knowledge base of manufacturers has greatly increased over the last ten years from ubiquinol’s launch; therefore, we are at the starting point of seeing ubiquinol-anchored formulations proliferate in the market.” Brands selling supplements made with Kaneka QH ubiquinol include NOW Foods, Puritan’s Pride, Jarrow Formulas, Doctor’s Best, Life Extension, and Healthy Origins.

CoQ10 for Dietary Supplements Market Update

Omega-3, CoQ10 May Benefit Prostate Health, Study Shows

Prakash, S et al. “Role of coenzyme Q10 as an antioxidant and bioenergizer in periodontal diseases.”

TÃ³th, Å  et al. “Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.” 

Journal of Basic and Clinical Physiology and Pharmacology,

A look at why CoQ10 has remained a go-to heart health ingredient for decades.

CoQ10: An Update on an Old Standby

Is milk by any other name really milk? Not if the 32 lawmakers who signed a letter to FDA requesting that the agency ban the term “milk” from the labels of non-dairy “milks.” In a missive dated December 16, 2016, the House members argued that dairy milk is uniquely nutritious, and that by assuming the name “milk,” less-nutritious nondairy alternatives mislead consumers.

Whether you buy their argument or not-and FDA, for its part, has yet to take sides-the mere fact that these busy politicians are making it underscores the influence of the dairy industry and the competition it faces from nondairy products. That competition extends beyond the milk case to the protein category, where nondairy plant-sourced options ranging from pea to hemp are chipping away at the primacy dairy protein has long enjoyed.

The dairy industry isn’t taking the challenges lying down, however. After all, it still has a compelling story to tell. Says Kate Sager, marketing manager-America, Ingredia, Inc. (Wapakoneta, OH), “Dairy proteins have been around for a very long time and are industry standards. We do believe that even with the noise that plant proteins are making, animal proteins-and dairy specifically-will continue to dominate the marketplace into the future.”

The protein marketplace is a crucible of dynamism, regardless of who is dominant. Citing data from the International Food Information Council Foundation’s (IFIC) 2016 Food & Health Survey, Kara McDonald, vice president of global marketing communications, U.S. Dairy Export Council (USDEC; Arlington, VA), notes that 64% of U.S. adults proactively tried consuming more protein in 2016.

Looking specifically at dairy-derived whey, BCC Research forecasts the global market to hit $13.5 billion in 2020, compared with $9.2 billion in 2015, representing a compound annual growth rate of 6.5% for the period.

Notes Pernille Dorthea Frederiksen, health concept developer, Arla Foods Ingredients (Viby, Denmark), “This is testament to the strength of whey as a protein proposition.”

As with most trends, the passion for protein is evolving. McDonald notes, “Consumers are ‘siloing’ protein’s benefits for more personalized nutrition.” Mainstream audiences are also “more knowledgeable than ever” about its health benefits and are “looking for convenient high-protein products to help them manage their weight,” she states; meanwhile, more active fans “are looking for sports nutrition beverages to complement their daily workouts.”

Regardless of what consumers are looking for, Sarah Staley, vice president of performance nutrition, FrieslandCampina Ingredients North America, Inc. (Paramus, NJ), cites a Mintel report

 when she states, “We can see that it remains the most-searched-for term in the United States when seeking healthy products.”

Consumer interest in protein remains strong for good reason. Protein is a critical source of dietary energy, supplying the same 4 kcal/gram that carbohydrate does. But, protein also supplies something else: amino acids, the building blocks of individual proteins and the body’s tissues. “Muscle, skin, bones, organs and the brain, as well as hormones and other components involved in how our bodies work,” notes Angela Rowan, general manager nutrition, Fonterra Co-operative Group Limited (Palmerston North, New Zealand).

Nutrition-savvy shoppers-and, increasingly, everyone else-have grown wise to this. Notes Rowan, “Most consumers know that protein is an important nutrient that supports muscle health and strong bones, and some even recognize that it can help keep you feel fuller longer.” But what they may not know, she says, is “how much they should be eating, when throughout the day they should be eating more protein or which are the best dietary sources.”

And that’s where the flood of plant proteins on the market complicates things. Observes McDonald, “Plant sources seem to get a lot of attention in the media, partially because of the ‘newness’ element.” And as with plant-based “milks” striving to measure up to cow’s milk-which they cannot do without heavy fortification-“protein alternatives are also striving to be like dairy,” she notes.

Such “imitation might be the sincerest form of flattery,” McDonald says, but companies that are eager to promote plant-based protein “may rely on consumers’ lack of understanding of the complex differences in amino acid makeup and nutritional density that set dairy apart” to hold onto that newfound attention, she contends.

Then again, it would be unfair to ascribe consumers’ interest in plant-based proteins entirely to misunderstanding. Concern for animal rights, support for sustainable sourcing, unease about potential antibiotic residues in milk, and a growing awareness of dairy allergies all stoke plant protein’s popularity, notes Staley. “We also see that consumers have the perception that plant proteins may be more natural and perhaps ‘better for you’ than proteins from other sources,” she says. Regardless of whether or not that’s the case, what is true is that “consumers want to make better choices, and there’s widespread understanding that protein is good for them,” says Staley.

In such a pro-protein environment, dairy has every reason to thrive, even with the stiff competition that plant products mount. As Frederiksen says, such competition is “to be expected, and it’s been good for the overall profile of protein as a nutrient.”

It’s as a nutrient, in fact, that dairy proteins most markedly stands out. “High-quality protein,” McDonald says, “is dairy’s strength.” While all proteins comprise amino acids, dairy contains all the essential amino acids (EAAs) that our bodies need for growth and recovery. What’s more, dairy’s amino acids are “of high bioavailability,” Rowan says, “so they’re readily digested and absorbed to be used.”

Dairy protein also outperforms as a source of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. BCAAs, and leucine in particular, play “an important role in stimulating muscle growth,” Rowan continues. This helps explain why dairy protein is a sports-nutrition must-but Rowan points out that one does not to be training for an athletic event to benefit: “As our muscles are continuously turning over, consuming rich sources of these amino acids can be a valuable strategy for all ages and lifestyle, from athletes and body builders to the healthy aging and those looking to maintain muscle mass for optimal wellbeing.”

comparing the digestible indispensable amino acid scores (DIAASs) of whey protein concentrate, whey protein isolate, milk protein concentrate, skimmed milk powder, pea protein concentrate, soy protein isolate, soy flour, and whole-grain wheat ranked all dairy proteins “excellent/high” in quality for people ages six months and older, soy isolate and flour as “good,” and pea and wheat significantly lower.

 The lesson: “You’d simply have to consume a lot more plant protein to get the same nutrition you’d get from non-plant sources such as dairy,” Staley says.

New processing technologies are letting suppliers enhance dairy proteins’ nutritional profile even further, with micellar casein concentrate (MCC) a prime example of what the innovations can achieve. Staley’s company uses a gentle cold-process filtration to produce a micellar casein ingredient that “retains a native-state micellar structure similar to fresh milk,” she explains. “This unique ingredient is proven to be the slowest-releasing protein source, resulting in a positive amino acid net balance and, thus, improved muscle recovery.”

Indeed, as a recovery aid, slow-digesting micellar casein “sits apart from all other dairy and plant proteins,” Sager adds. Because it bathes post-exertion muscles in a prolonged supply of amino acids for growth and repair, she says, athletes who use it “are ready for their next training session.” Even better, its long arc of digestion adds to its weight-management appeal, as it both makes people feel fuller-like all proteins-and extends that feeling over time.

MCC is a handy ingredient for processors, too. McDonald points to functional benefits like wetting, dispersability, heat stability at neutral pH, and solubility. Sager notes that her company’s powdered form of the ingredient dissolves readily and tolerates heat up to ultra-high temperatures (290 °F). “In comparison,” she says, “plant proteins don’t always dissolve, can denature with high heat and can produce a very gritty texture.”

Another plant protein disadvantage: They don’t always taste so great. Consumers often label their taste as “beany,” “brothy,” “strong,” “earthy,” and “bitter.” Although masking systems somewhat overcome plant’s characteristic off notes, they rarely do the whole trick and can muck up the “clean” labeling that drives so many consumers to plant proteins in the first place.

Dairy proteins, on the other hand, call to mind terms like “mild,” “neutral,” “clean-tasting,” and-obviously “dairy-like,” which “makes them acceptable to most consumers” and “easier to formulate into a wider range of palatable products, from snacks to dairy proteins to beverages,” Frederiksen says. This versatility “is a real benefit if you’re looking to target as many shoppers as possible,” she notes.

So, with a flavor that’s complementary rather than overpowering-plus superior nutrition, novel ingredient options, and functional properties ranging from emulsification and foaming to water binding and gelation-what could dairy proteins possibly still be missing?

If you’re thinking, “a clean and green narrative,” you’re wrong: they’ve got that, too. Says Frederiksen, “Dairy proteins like whey have a great story to tell.” McDonald agrees, adding that “the sustainability element is probably the most misunderstood element that seems unnecessarily to sell dairy short.”

Dairy proteins receive criticism for the heavy resource input their production entails. But, says McDonald, “Food systems are complex. Not only should the resources needed to make a food be considered, but the unique nutritional value it delivers should be weighed, too.”

On top of that, “If you haven’t visited a local dairy farm since elementary school,” she adds, “you might not realize the intense management to ensure the cows’ health and comfort.” After all, dairy farmers gain no margin mistreating their key asset.

Making the case for dairy proteins in a plant-protein era.

Nutritional Outlook Vol. 20, No. 9

Bolstering Botanical Best Practices

Setting the Cereal Bar High

Natural Color Stability: Challenges and Opportunities

Smart Ingredients for Brain Health

CoQ10: An Update on an Old Standby

Milk Matters: Dairy Protein versus Plant Protein

Innovative New Delivery Systems for Dietary Supplements

Whey Protein Benefits for Weight and Heart Health

What’s Driving Collagen?

10 Protein Myths Debunked