More consumers are embracing plant-based foods and the idea that consuming less animal-based products will improve their health and the health of the environment. U.S. retail sales of plant-based foods grew 27% to $7 billion in 2020, according to SPINS data commissioned by the Plant Based Foods Association and the Good Food Institute.

Plant-based meat is the second largest category of the plant-based food market, after plant-based dairy, increasing in sales by 45% to reach $1.4 billion in 2020. Plant-based meat sales grew twice as fast as conventional meat sales, accounting for 2.7% of retail packaged meat sales. More specifically, refrigerated plant-based meat sales grew 75% in 2020, and frozen plant-based meat sales grew 30% in 2020.

It’s clear that in the years to come, as ingredient suppliers and manufacturers continue to innovate, plant-based meats will take up more and more valuable retail space in the refrigerated and frozen foods section, developing greater parity with conventional meats. Food technology innovations and consumer curiosity are accelerating growth.

As more consumers search out meat alternatives that give them the experience of eating meat without the guilt, another player may complicate matters further: cultivated meat.

Cultivated meat is meat grown in a lab. Cells are isolated from animals, and these cells are grown to form tissues. While it sounds like science fiction, cultivated meat is a reality and may offer a humane and environmentally friendly way to consume actual meat. For example, Israel-based 

 has successfully grown thin-cut beef steak using non-GMO cells isolated from healthy cows. “Our products mirror the sensory quality, texture, flavor, and fatty marbling of a conventionally produced steak,” explains Didier Toubia, co-founder and CEO of Aleph Farms. “Compared to plant-based alternatives, Aleph Farms’ cultivated meat incorporates the same amino acids and volatile compounds, and the same enzymatic reactions occur during cooking.”

Aleph says it will be able to expand its portfolio to cultured meat products cultivated from the cells of various animal species. The company has even developed a platform that allows it to produce any meat cut of any size through an approach called 3D bioprinting. Although cells are taken from animals, there is no need for repeated cell collection from livestock. For example, Aleph has created frozen cell banks from a single cell isolation to serve as a source for thousands of tons of meat per year.

One of the biggest obstacles facing cultivated meat is accomplishing large-scale production for a cost that is in line with the meat industry. Building consumer trust is another, says Toubia. For its part, Aleph is scaling up, building a pilot plant it calls BioFarm, in Israel. The company plans on completing the pilot plant in 2022 and launching its first product, the thin-cut beef steak, that same year. It is also actively working on regulatory approvals and building up its supply chain.

So far, the only regulatory approval for cultivated meat has been in Singapore, but that was an important step in the category’s progress, says Toubia. “It isn’t a long-term vision anymore but rather a practical solution to some of our most urgent issues today associated with food production. This milestone represents the ongoing process of bringing cultivated meat products to global markets,” he says. “We value the regulator as a partner to build trust with the consumers. We’ve been interacting with the USDA and FDA for the past three years and believe that the U.S. will be one of the first countries to clear cultivated meat for marketing.”

When it comes to consumer trust, Aleph is optimistic. According to a survey commissioned by the company, there is a high level of openness toward cultivated meat, despite its novelty. The survey, which included 4025 respondents from the U.S. and UK, found that 40% of respondents from each country considered themselves to be at least somewhat likely to try cultivated meat or extremely likely to try cultivated meat. In addition, 44% of respondents from each country considered themselves somewhat likely to buy cultivated meat. Familiarity and support for the technology was higher among Gen Z and millennials, but genuine curiosity pervaded all generations.

Another important statistic to consider is that, according to a survey from the research firm Mattson in 2017, 29% of consumers identified as “flexitarian,” actively reducing the amount of meat in their diets but not cutting it out entirely. Will these consumers pick plant-based meat replicas once they have access to kill-free, lab-grown meat? Or, once the novelty wears off, will all these products just be another option? It’s too early to make predictions about the future of cultivated meat and the impact it may have on the market, but it’s a significant, if not controversial, innovation that will captivate some, repulse others, and all the while draw even more attention to meat alternatives.

Articles

Plant-based meat is growing rapidly, but with cultivated meat on the horizon, the meat aisle will get even more competitive.

Is meat the new meat? The rise of cultivated meat

Small as they are, seeds and plantings play a big role in the success of finished health products. If chosen carefully and tended to properly, they ensure the integrity of finished health products—that what’s on the label is actually in the bottle. And the more efficiently they are grown, the more cost-effective they can be. By using traditional breeding methods with increasing sophistication, today’s farmers are catering their crops to high yields and other selective attributes.

Whether in need of a high-yielding, cheap food crop or a specialized botanical ingredient that’s very rich in a certain compound, seed breeding offers great possibilities within the limits of mother nature. It’s a business that caters to its customers now more than ever before.

Seed breeding programs are most commonly associated with staple food crops. The need to feed a growing world population inspires the public and private sector to develop new cultivars of existing crops that can produce more food on less land, be it plants with more edible seeds, fruits, leaves, and/or roots. Legumes and grains receive much attention because they are rich in vital protein. And one Israeli company is working to improve more than just the harvest yields of legumes and grains.

Equinom Ltd. (Givat Brenner, Israel) uses natural breeding methods and a unique computational breeding technology to make its seed breeding discoveries. “This enables us to improve multiple traits controlled by multiple genes,” says company founder and CEO Gil Shalev. “Our technology is the only technology that can do this. Other non-GMO companies do not use genome discoveries at all and, in most cases, the volume of the seeds for those markets are limited or using common technologies which were developed for improving single traits—namely yield.”

While Equinom’s efforts are producing soy beans, yellow peas, and similar products with competitive yields, they also promise higher amounts of protein than conventional alternatives and the ability to select seeds based on customer-specific needs, including texture, taste, and starch function. By considering these characteristics at the seed stage, Equinom is giving food companies the opportunity to select ingredients from an extensive bank of traits—whichever best appeals to product development needs.

Equinom’s unique breeding program is also targeting sesame. Having developed a sesame seed that’s resistant to shatter, the company is able to improve yields by reducing the amount of seed loss during harvest of these delicate seeds. An improved sesame seed, with its mild nutty flavor and hypoallergenic status, allows sesame to replace other legumes and grains like soy and wheat, both common allergens, in the flour, oil, and protein concentrate markets.

Other projects at Equinom center on less popular grains and beans, such as cowpeas, mung beans, and fava beans, and are tailored to local climates and cultural recipes.

Though traded at much lower volumes than foodstuffs, medicinal herbs are of great importance to the global dietary supplement industry and so receive their own significant research investments. Yields are important, but they can depend on which part of a plant is most needed by a customer. Since certain plant compounds can be concentrated more in one part of the plant than another (e.g., the roots vs. the leaves), breeding depends on what a customer wants.

Native Botanicals Inc. (Banner Elk, NC) is a supplier of botanical raw materials, and it relies on partnerships with farms to produce hundreds of plants that are uniquely catered to each customer. In consideration to mountain arnica, company president Edward Fletcher says that some of his customers just want arnica flowers. “So we pick out the plants that produce bigger and more flowers, and we propagate them,” says Fletcher. “We have them in one section of our fields, and we just harvest the flowers.” Other arnica plants may be selected for a combination of high foliage and flowers or a higher number of roots. Particular parts of arnica may be concentrated in certain active compounds for which companies want to standardize their products. And that goes for all other plants.

Horticulturally, farmers can stress plants to increase the production of their precious compounds outdoors and in greenhouses, but mother nature often has its limits. In some cases, plants grown in the wild may have constituent levels that can’t be easily duplicated in a cultivation setting. Wild harvesting may be necessary.

As the world’s climate changes, breeding projects are focused on plants that can adapt to warming climates and less water. Natural selection plays a part in this, as well. Agricultural practices need to change, and farmers are aware of this and making changes, such as irrigating more efficiently, which can benefit their own bottom-line finances.

Fletcher at Native Botanicals Inc. offers a good rule of thumb: try to adapt to where each species is native and how it best grows. Create a clear line of communication with farmers and natives who have been growing these plants for generations.

In order to procure the correct ingredients for any formulation, manufacturers should share their full specification sheets with ingredient suppliers and growers. When switching from one supplier to another, provide your new supplier with a raw material sample (if available) that best exemplifies your needs in cut size, color, and/or content. Share information on how previous suppliers may have failed to meet certain expectations. And don’t ignore post-harvest handling and storage factors. A satisfactory crop, farmed to specification, can be compromised in handling, shipping, and/or storage.

Seed breeding is a business that caters to its customers now more than ever before.

Seed breeding for today’s foods and dietary supplements is an increasingly customer-focused experience

“Are we almost there?” It’s the question U.S. hemp cannabidiol (CBD) and dietary supplement firms have been asking for years.

Whether CBD will become a legal dietary ingredient in the U.S. this year—or next year, or the year after that—has been a frustrating guessing game for stakeholders. Now, with legislative bills either introduced or reintroduced in the U.S. House of Representatives (“

The Hemp and Hemp-Derived CBD Consumer Protection and Market Stabilization Act of 2021

 from Senate Majority Leader Chuck Schumer (D-NY) and other democratic senators, those hoping for CBD’s legalization in supplements are excitedly wondering whether this time around, change will actually come.

Even as they wait, there’s plenty companies can do now to prepare—and they should. Once CBD gets the green light, companies need to be able to implement their go-to-market plans quickly, says Ashish Talati, partner at Amin Talati Wasserman LLP (Chicago).

Talati was the inaugural guest of our brand-new 

. He discussed what his clients and others in industry have been doing to prepare.

“Companies should be reacting and acting right now,” Talati said in our interview. “Whether there is legislation sometime this year, or next year, I certainly think the momentum has been pushed. We have two active bills and possibly a third one, so certainly companies should be reacting to it. One of the things that will come out of this is: Does a company need to file New Dietary Ingredient (NDI) notifications for dietary supplements, or is there a Generally Recognized as Safe (GRAS) pathway for foods if [CBD] is allowed in the food supply?”

Safety studies are the basis of both NDI notifications and GRAS conclusions, so companies have little to lose by investing in those safety studies now, acting on the assumption that CBD will be legalized in the supplements market at some point. “Either GRAS or NDI—they’re safety conclusions,” Talati said. “The foundation will be the same.” Even if a company is waiting to file an NDI notification with FDA until CBD’s legal status is certain, completing those safety studies ahead of time is smart.

Safety studies, after all, take time to conduct. “Regardless of what they decide to do, certainly right now, what we recommend to companies is to go through the whole motion,” Talati said. “So, if you want to go down the GRAS path, have the studies done. Have them published—a 90-day subchronic study. Have the GRAS dossier drafted. Have the expert panel review and sign off.”

Unfortunately, if companies haven’t already started, they might already be behind. “A lot of the groundwork should have been done,” Talati said. “If someone’s reacting right now, they’re probably not going to be the first ones…I have clients that have basically completed a lot of that and who are just ready to file if they have to file NDI notifications or completed GRAS work. A lot of that work has been done by some of the companies already because they want to be the first ones out the gate, so to speak.”

Companies should also be vetting their suppliers for readiness. “You should be asking some tough questions,” he said. “What are they prepared to do? It’s very important that your supply chain can react to [regulatory changes]. And then be prepared…if a supplier is not able to do it, or if you can tell they have not really done anything [to prepare], then be able to switch to another supplier. The market will have multiple suppliers that have completed [this regulatory work] and are willing to complete the process.”

For more insights like this, be sure to check out The Nutritional Outlook Podcast. In each month’s episode, I, along with

editor Sebastian Krawiec, will dig deeper into key issues impacting the dietary supplement, functional food, and natural products industries. We’ll be interviewing many of the experts whose advice has informed our readers year after year. Visit 

 for more information. We look forward to seeing you there.

Bad news for CBD: FDA objects to two NDI notifications for full-spectrum hemp ingredients

What can U.S. companies do now to prepare if CBD is legalized for dietary supplements? An expert advises.

CBD’s legal future: How can you plan for success now?

In a vast health products marketplace with many competitors, product claims have great value and can make all the difference in product sales. But dietary supplement manufacturers need to tread lightly when making express or even implied health claims. If health claims aren’t adequately substantiated, history shows that warning letters and lawsuits are a likely risk.

How should supplement manufacturers and marketers handle the subject of pain relief? It’s a common concern among consumers. Many of the ingredients used in today’s health product formulas have been associated with reduction in self-reported pain and related biomarkers in published research. But is that enough?

In recent months, even products featuring ingredients as common as magnesium sulfate and glucosamine have been the focus of class action lawsuits. So, what’s the safest way to navigate pain-relief health claims in a well-policed industry, and how can brands substantiate their claims?

While a disgruntled consumer or overzealous litigator may be the first person to notice a pain-relief claim that could be called into question, the official power to make judgements comes down to FDA and FTC. Though FDA controls the advertising and labeling of foods, drugs, medical devices, and cosmetics, every pain claim doesn’t require FDA approval. It’s ultimately up to FTC to assess the truth or falsity of all advertising.

“Independent of FDA regulations, advertising claims must be truthful under the FTC Act,” says Laura Brett, vice president of the National Advertising Division at BBB National Programs (McLean, VA), an independent nonprofit organization that evaluates all forms of advertising. “In other words, whether a product is making a claim that complies with FDA regulations is a separate question from whether it is making a claim that is truthful and substantiated.”

“Moreover,” she says, “there are other attributes related to the nature of a product’s pain relief that may not be covered by its FDA regulatory scheme, which companies may tout to consumers.” Two examples are onset of action (how quickly a product provides relief) and duration (how long the pain relief lasts).

For any pain-relief claims, ranging from general pain relief to the duration of pain relief, scientific substantiation is required to the extent that experts in the field believe is reasonable, says Brett. Generally speaking, the gold standard for substantiation would be double-blind, randomized, placebo-controlled human clinical testing that demonstrates the product’s effect on pain. Fail to do this or present evidence of such testing on an identical product, and you may run the risk of misbehavior.

But a gold standard test isn’t the only way to establish a reasonable basis for a claim.

“If you have less evidence, a prominent disclosure about the amount of evidence you possess for a claim could help set reasonable expectations about the product,” says John E. Villafranco, partner at Kelley Drye & Warren LLP, a law firm with significant expertise in the dietary supplement industry.

The more precise a brand can make its research and messaging to consumers, the better.

How pain relief is conveyed is not as important as the content of the message. Whether a claim is expressly stated on a product label or website, or implied through pictures, video, and customer testimonials, Brett says that if the consumer takes away a message that the product relieves pain, the brand must comply with FTC’s standards for scientific substantiation.

Apart from avoiding any suggestion that a product diagnoses, cures, mitigates, treats, or prevents a disease (“prevents arthritis pain”) or its characteristic symptoms (“joint-pain relief”)—all of which qualify as disease claims—it’s most important that brands stick to specific claims that they can substantiate.

“And when you do have substantiation, make sure you don’t say more than you can show,” says Villafranco. “For example, if your study shows your product reduced soreness, stick with that rather than stating your product eliminates it.” Soreness, aches, and sunburn are specific kinds of pain that, if well substantiated, make brand messaging less open to interpretation and accusation.

Again, all marketers of ingredients and finished products must consider the consequences of a false claim and create their brand messaging appropriately.

How can you market pain-relief dietary supplements while staying on the right side of legally permissible health claims?

Pain Claims: Navigating pain-relief supplement claims

: It’s a saying—and a strategy—that plenty of us have grown familiar with over the past year and a half.

And who could blame us? In the midst of a year that’s rendered words like 

 cliché, it’s only natural to seek comfort. And at a fundamental level, comfort is a lot of what eating is about. (Just ask any recently fed baby.)

But while some have found their emotional Band-Aid in a bowl of ice cream or homemade brownie, others seek a more mindful approach to eating their feelings.

In so doing, they’re inspiring wellness brands to use foods and beverages as vehicles for destressing, calming, and sleep-promoting ingredients—ingredients that have heretofore been the province primarily of supplements. The results are gaining traction and putting a scientifically substantiated spin on the concept of “comfort food.”

The reawakening to wellness that consumers experienced in 2020 will go down in history as one of COVID-19’s unanticipated side effects. But just as striking, says Itay Shafat, cognitive health product manager, IFF Health (New York City), was the “holistic” tone that reawakening took.

“It’s remarkable how much consumers have shifted from centering their idea of health and well-being around the physical alone to recognizing that mental and physical health complement each other,” he notes. And that recognition won’t go away with the coronavirus.

Why? Because the stress, anxiety, poor sleep, and even sadness plaguing the collective psyche of late merely amplify emotions that modern society’s been managing for generations now.

Consider that while Kaiser Family Foundation 

 show that as many as four in 10 American adults reported symptoms of anxiety or depressive disorder during the pandemic, a notable 11% were already reporting those same symptoms in the January-to-June period of the previous year.

“Thus,” Shafat concludes, “continuing to address issues like stress and sleep are of the utmost importance.”

Julia Díaz, head of marketing, Pharmactive (Madrid), agrees. “The world is still awaiting full recovery from this crisis,” she points out. “So maintaining mental strength to cope with the ‘new normal’ atop all the pandemic’s lingering effects remains a must-have for consumers.”

Demand for stress-management, mood-support and sleep supplements reflects that must-have status. 

 reported a 35.7% increase in sales of such products across mass and natural channels year-over-year, with their take totaling nearly $400 million from January to June of 2020, compared to $294 million for the same period in 2019.

But supplements are only where the story gets started. According to a 2020 FMCG Gurus survey on the pandemic’s effects—conducted for functional-ingredient supplier Beneo (Parsippany, NJ)—55% of consumers in the market to improve their mental well-being are likely to opt for a food or drink as a means of doing so. And a whole constellation of factors drives them toward that decision.

Pill fatigue, of course, is one, as is the aforementioned practice of comforting oneself with food and drink.

“It’s well known that tasty foods exert a comforting effect and are widely adopted coping mechanisms,” Díaz notes. And with some continuing pandemic restrictions extending consumers’ sense of cabin fever, “the temptation to snack becomes even greater,” she says.

Shafat notes that mood foods and drinks make the most sense when their constituent ingredients connote an association with calm and relaxation. “In the case of stress, for example,” he says, “teas made with chamomile, lemon balm, cinnamon, rhodiola, and other extracts with proven, or at least publicly accepted, benefits can help to address it.”

Díaz detects an echo between consumers’ adoption of mood foods and “the growing awareness of self-care and healthy habits,” which she says can include everything from choosing organic produce to reducing sugar consumption.

And Shafat cites a very practical reason for using food to improve mood: “Many active ingredients are better absorbed when taken with food,” he says. “And liquid formats like beverages move more quickly through the GI tract.” By contrast, supplement capsules and tablets must disintegrate first before allowing their actives to dissolve and the body to absorb them, he says.

As for which mood-improving ingredients are getting play in food and beverage formulations, both Díaz and Shafat shine a spotlight on botanicals. Díaz sees the plant-based ingredients as capitalizing on their “long history of traditional use to aid sleep and induce calm.” That history not only strikes consumers as “natural” and evokes their trust; on the manufacturing side, it can also relieve brands of the regulatory concerns surrounding ingredients like CBD.

Díaz notes that sales of Affron, Pharmactive’s natural saffron (

 L.) extract, have been rising in concert with demand for calming formulations.

Previous clinical studies have established its capacity to support mood and relaxation, relieve stress and improve sleep, she notes, while adding that a recent clinical study

 of 12- to 16-year-olds with mild to moderate anxiety and depression showed that subjects who took the extract over an eight-week period experienced improvements in symptoms.

The extract’s proposed mechanism of action rests on its antioxidant and anti-inflammatory properties, which may help balance levels of key neurotransmitters like serotonin and dopamine while also fighting the oxidative stress that anxiety and stress can trigger in the brain.

Meanwhile, Shafat looks to the gut-brain axis for further hints as to where mood food may be headed.

“As consumers begin to understand the connection between our brains and our microbiome more widely,” he says, “the category of probiotic-fortified foods and beverages for stress and mood should grow.”

Probiotics are already building a track record in this arena. A randomized, double-blind, placebo-controlled study

 involving 120 healthy subjects aged 18 to 45 found that IFF’s Howaru Calm probiotic (

 Lpc-37) improved psychological and physiological markers of stress and anxiety in subjects who took the ingredient.

“That’s a big development,” Shafat says. “It gives consumers a scientifically proven way to manage daily stress by taking a probiotic they can buy online or in a store.”

Formulators will have to approach the task of developing mood foods and beverages differently from how they’d build a traditional supplement. As Shafat cautions, “Adding any functional ingredient to a food or beverage poses challenges to processing, shelf stability, solubility, taste, and more.”

And as any food or beverage developer knows, “Consumers drink and eat what’s tasty,” Shafat says. “That’s driving the industry’s focus toward adapting these ingredients—many of which are bitter—to foods and beverages using ingredients like flavor maskers.”

It’s not just product appeal that hangs in the balance, either; it’s consumer compliance. After all, a mood-enhancing food or drink will only work if consumers feel compelled to consume it on the regular. “These products have to be linked to daily, rather than occasional, consumption,” Díaz says. “Natural solutions usually work better this way.”

Brands also must remain measured in making promises for their products. Díaz reiterates the importance of drawing hard lines at claiming to diagnose, cure, mitigate, treat, or prevent disease. And she encourages brands to support any claims they do make with rigorous scientific evidence.

As research into mood-enhancing actives proceeds, that evidence will only mount. Says Shafat, “New research on mood and relaxation is taking place to offer more substantiation for active ingredients. This will result in more acceptable mood-food and -beverage formulations for both the industry and consumers.”

Panchal N et al. “The Implications of COVID-19 for Mental Health and Substance Use.” Kaiser Family Foundation website. Published February 10, 2021. 

Daniells S. “Stress Management Supplements Sales Surge with Sleep and Adaptogen Lines Leading the Way.” Nutraingredients-USA.com. Updated August 18, 2020. 

Lopresti AL et al. “Affron, a standardized extract from saffron (

 L.) for treatment of youth anxiety and depressive symptoms: a randomized, double-blind, placebo-controlled study,” 

 Lpc-37® improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study).” 

Formulators will have to approach the task of developing mood foods and beverages differently from how they’d build a traditional supplement.

Comfort Food: Foods and beverages deliver sleep, stress, and mood relief in turbulent times

Another cannabinoid has come onto the scene: Delta-8 THC. Yes, THC. The cannabinoid, which is naturally occurring in small amounts in hemp can be synthesized from cannabidiol (CBD) or delta-9 THC, the primary psychoactive constituent of cannabis. Unlike CBD, delta-8 THC 

 produce psychoactive effects in users, though reportedly not the same level of intoxication associated with delta-9 THC. Delta-8 THC can be found in multiple formats, including tinctures, function beverages, vapes, and gummies.

There has been a spike in delta-8 THC products because an 

 of hemp drove down CBD prices and synthesizing delta-8 THC became a way for farmers and extractors to use up that surplus and make their money back. Like with CBD, manufacturers have been comfortable manufacturing and selling products with delta-8 THC because of the recent 

, explains Felicia Leborgne Nowels, partner, government affairs and public policy at the law firm Akerman.

The 2018 Farm Bill removed hemp from the jurisdiction of the Drug Enforcement Agency (DEA) as a controlled substance, and put the U.S. Department of Agriculture in charge of the cultivation and harvest of the plant. Specifically, the Farm Bill made a distinction between hemp and marijuana, defining hemp as plant 

 L., or any part of the plant, including the seeds, derivatives, and extracts with delta-9 Tetrahydrocannabinol (THC) levels that do not exceed 0.3% by dry weight. Of course, no threshold or restrictions were placed on delta-8 THC.

“The problem that we’re now seeing is that in the Fall of 2020, the DEA issued an 

. In that interim final rule, they included statements discussing synthetically derived THC, and those would remain scheduled and a controlled substance,” says Nowels. “The confusion is: delta-8 THC is hemp-derived so it should not be scheduled – it’s outside of the DEA purview – but what is the definition of ‘synthetically derived’?”

Specifically, the interim final rule states: “The AIA [Agriculture Improvement Act of 2018] does not impact the control status of synthetically derived tetrahydrocannabinols (for Controlled Substance Code Number 7370) because the statutory definition of ‘hemp’ is limited to materials that are derived from the plant 

 L. For synthetically derived tetrahydrocannabinols, the concentration of Δ9-THC is not a determining factor in whether the material is a controlled substance. All synthetically derived tetrahydrocannabinols remain schedule I controlled substances.”

Because DEA does not provide an explicit definition for synthetically derived tetrahydrocannabinols, there is room for interpretation, and since hemp is no longer a controlled substance, proponents would argue that delta-8 THC derived from hemp is not a controlled substance either. As of right now, FDA has not taken any enforcement action against delta-8 THC products, but that does not mean it won’t do so in the near future. Unlike CBD, delta-8 THC has not been investigated as a new drug and therefore does not fall under FDA’s drug exclusion rule. However, it has not undergone any pre-market regulatory process, such as new dietary ingredient notification, either.

“As to whether the FDA will address delta-8 vs. delta-9 [THC]; I think that’s going to be considered altogether. I don’t think FDA will look at delta-8 in a vacuum alone,” says Nowels.

 are taking matters into their own hands. Currently, there are 11 states which ban delta-8 THC entirely: Alaska, Arkansas, Arizona, Colorado, Delaware, Idaho, Iowa, Mississippi, Montana, Rhode Island, and Utah. State regulators in Kentucky and Vermont have also clarified that their position on delta-8 THC is that it is a controlled substance. Illinois, North Dakota, and Oregon are considering legislation to ban the sale of delta-8 THC, and the Washington Liquor and Cannabis Board has temporarily banned synthetic hemp ingredients.

Considering the lack of regulatory clarity, a patchwork of state regulation, and the fact that delta-8 THC products may be intoxicating, the American Herbal Products Association (AHPA; Silver Spring, MD) recently issued a new guidance policy discouraging “the marketing of goods for consumption by any route” that contain synthesized cannabinoids such as delta-8 THC or artificial cannabinoids. AHPA defines synthesized cannabinoids as “a cannabinoid synthesized in a laboratory or by industry using directed synthetic or biosynthetic chemistry rather than traditional food preparation techniques such as heating or extracting. They may be nature-identical or artificial since this definition refers only to the process of their creation.”

AHPA’s definition of “artificial cannabinoids” is “any cannabimimetic compound that interacts with cannabinoid receptors but whose molecular structure is not found in nature.”

The hemp-derived product industry is not slowing down. CBD and delta-8 THC are only two of several cannabinoids present in hemp, many of which are already making their way to the market, such as 

. While FDA maintains its position on CBD, and is 

, the current marketplace demands more substantive action to protect consumer safety. Legislation may be the solution, but gridlock in Congress prevents the swift passage of laws. In the meantime, demand grows, the industry grows, and regulators remain a few steps behind.

Delta-8 THC is a new cannabinoid that has come to market, testing the legal boundaries of hemp-derived cannabinoids.

What is delta-8 THC and is it legal?

Like a piping-hot press-pot full of freshly brewed French roast, activity in the RTD coffee space is, in a word, 

. Refrigerated options alone posted growth of nearly 20% for the 52 weeks ending May 17, 2020, with steady growth projected through at least 2025, according to Chicago-based market-research firm IRI.

And it’s a sure bet that plenty of the products driving that growth fall into the class of creamy, candy-sweet concoctions that resemble dessert more than they do a morning pick-me-up.

But another contributor, observes Ilana Orlofsky, senior marketing manager at beverage-development company Imbibe (Niles, IL), are coffees “with health-oriented benefits,” as a growing cadre of category disruptors is capitalizing on coffee’s better-for-you cred by using it as a base for functional formulation.

And they’re doing so for one simple reason, Orlofsky says: “Consumers are open to coffee as a platform for enhancing wellness.”

It wasn’t always this way. Some of us remember a time when coffee bore the whiff of an illicit brew that was safe—if it was safe at all—for grownups only.

“People said coffee could cause all sorts of problems,” recalls James S. Tonkin, founder and president of beverage-development firm Healthy Brand Builders (Scottsdale, AZ). “It would stunt your growth, cause heart problems, turn the inside of your body into a brown mess,” he says. “People considered these truisms, but they were just anecdotes.”

Now, he says, “There’s a lot we know about coffee’s benefits, from helping to [reduce the risk of developing] Parkinson’s disease to contributing to emotional well-being.”

Even coffee’s caffeine—long demonized for causing any number of ills—is proving demonstrably to be both a legitimate mood-lifter and a performance-enhancing drug.

“After you drink coffee,” explains Stipe Rezic, CEO and founder, Mushroom Cups (Solin, Croatia), “the caffeine is absorbed into the bloodstream and travels to the brain where it blocks an inhibitory neurotransmitter called adenosine.” With adenosine thus blocked, Rezic continues, neurotransmitters like norepinephrine and dopamine can flow more freely, “leading to enhanced firing of neurons. So coffee definitely positively affects your brain function.”

Moreover, he adds, “Several studies show that caffeine can boost metabolic rate, which leads to a fat-burning effect.” From his perspective, that makes coffee a tonic for sedentary desk jockeys: “While your body is still, coffee pushes your metabolism to move.”

And this is just the tip of the iceberg. Tonkin praises current research into coffee’s constituent phytonutrients, “and I think we’ll see a lot more coming out,” he says, “because the findings are real.”

In anticipation, brands keep innovating. Just ask Orlofsky. “If you step into the labs at Imbibe on any given day,” she says, “you’ll find product developers, flavor chemists, and taste-modulation experts working on a handful of coffee products.”

Concepts range from plant-based alternative-dairy lattes—“and plenty of dairy ones, too,” she insists—to collagen-infused coffee drinks, adaptogenic brews, sparkling coffees, and more, many with a cold-brew base and a few that are even nitrogenated.

Also exciting, she finds, are innovations in adjacent categories, like creamers and barista milks. “Califia Farms launched a mushroom and oat barista milk including extracts from cordyceps and lion’s mane,” she says, “and we expect several more functional creamers and alt-milks for coffee to launch in the next 12 to 18 months.”

Adds John T. Musselman, vice president, sales and marketing, Phenolaeis (Cambridge, MA), “Certainly, immunity-promoting ingredients—vitamins C and D, zinc, and elderberry—are top of mind these days, and formulators will continue to include them in functional coffees.” And given coffee’s history as a mental and physical stimulant, he expects to see more formulations addressing mood, cognitive health, and exercise recovery alike. “Markets like sports nutrition and esports will be keen to embrace these functional coffees,” he predicts.

In addition to proteins, vitamins, and “good fats” like medium-chain triglycerides (MCT) oil, Orlofsky has her eye on a rising role for adaptogens—“especially functional mushrooms like chaga, reishi, cordyceps, lion’s mane, and turkey tail,” she says—in “coffees-with-benefits.”

Not surprisingly, so does Mushroom Cups’ Rezic. Why adaptogens? Because while coffee’s stimulatory effects on the central nervous system improve alertness, attention, and concentration, he says, “Caffeine also boosts cortisol and adrenaline production, both of which are stress hormones.” That’s why too much can raise heart rate and blood pressure, and even trigger cell damage.

Adaptogens like functional mushrooms normalize production of those hormones, “helping to modulate the body’s stress response so that it doesn’t overreact and deplete cells of energy,” Rezic says. “This helps explain why mushroom coffee has been growing at such a fast pace—all of coffee’s benefits, but no jitters or crashes.”

His brand leans on adaptogenic fungi like chanterelles, which he says are rich in vitamins and minerals and help convert food into energy and serotonin; chaga, with powerful antioxidants that act as strong anti-inflammatories; cordyceps, which he claims improves oxygen uptake and aerobic capacity; and lion’s mane, which can improve mood while supporting brain function with its “fascinating ability to regrow nerve cells,” he says.

Even better, not only are the mushrooms good for us; they’re good in coffee, too. The company uses mushroom extracts that Rezic says are “very hard to taste.” In fact, he believes they lend the beverages “a hint of the forest.”

As for preserving their bioactivity in the finished products—which are powdered instant coffees delivered in sachets—extracting the high-potency actives is actually harder on them than formulating and producing the powders themselves. “Once you have that,” Rezic says, “the only important thing is that the consumer uses hot, not boiling, water, and they’ll have an awesome mushroomchino.”

Rezic finds the mushroom world “absolutely fascinating” and thinks we’ve barely scratched its surface. “Discovering other species beneficial to human health and adding them to beverages is something I’m very excited about,” he says. “I’m looking forward to doing more of it in the coming years.”

For their part, Musselman and Phenolaeis are using functional formulation to reinforce coffee’s own suite of phytonutrients.

“Consumers and marketers are more aware of the health benefits derived from coffee’s phenolic compounds and antioxidants,” he notes, adding that palm fruit extract—the company’s “flagship ingredient and driving force”—delivers a unique array of polyphenols that “complement coffee’s native phenolics from a health perspective,” he says, “and have noticeable flavor synergies with it, too.”

They’ve deployed the sustainably grown botanical in freeze-dried, roasted, and ground single-serve and RTD coffees, he says, “and additional functional-coffee formulations will soon be available, with palm fruit extract joining other ingredients that promote immunity and mood-state benefits.”

In working with Phenolaeis’s partners on these innovations, Musselman concludes, “We’re excited to follow the developments. Functional-coffee applications like cold brews, protein-based beverages, and probiotic espresso shots are all examples of what makes this sector vibrant and well positioned for growth as consumers look at coffee in new ways.”

Formulation and opportunities for functional coffees are endless.

Eye-opener: Consumers embrace coffee drinks as platforms for functional nutrition

The business of conducting clinical trials is changing. Due to the current global pandemic, research organizations are being forced to change how they recruit and monitor participants in studies and how they conduct daily business in general. For all of the change and general public uncertainty around COVID-19, some companies may be wondering if now is the right time to budget for clinical research.

Upon close inspection, however, the changes spurred by the current health climate may be impacting clinical research in more positive ways than negative ones. According to some contract research organizations around the world, participant recruitment is up. Virtual technologies which already existed are increasingly being adopted. So long as companies are prepared for the unexpected, now may be as good a time as any to conduct clinical research.

There’s no denying that COVID-19 has created uneasiness in the general population. On top of that, massive unemployment and slowing or all-out closures of public transportation are unusual hurdles to normal business activity. These factors appear to be having the opposite effect on clinical research, though.

“The ongoing COVID-19 pandemic has favorably impacted the ability to conduct studies,” says William J. Rowe, president and CEO of Nutrasource (Guelph, ON, Canada), a contract research organization with expertise in foods, beverages, and dietary supplements. “Participants generally have more flexible schedules and availability during core work hours, and this supplemental income from participant stipends is also attractive.” In addition to more flexible participant schedules and the need for additional income, Rowe says that greater interest in health and wellness spurred by COVID-19 is also improving recruitment numbers.

While the pandemic has slowed business for many non-essential businesses, it’s important to remember that clinical trials are considered essential services. “We did not stop working even during the peak lockdown period,” says Kriti Chaudhary of Vedic Lifesciences (Mumbai, India), a contract research organization focused on foods and food supplements and with offices in India and California. “Only a certain sugar-management study was slightly delayed because diabetics are considered a vulnerable population and were asked to avoid leaving their homes.”

More people stuck at home seems to mean that more people are willing to volunteer themselves to clinical research. Chaudhary says this unique circumstance even created a rare opportunity for her organization to examine the effect of the lockdown on human health in the elderly (knee pain in particular). But what happens when quarantining participants need to be seen in person for reasons such as drawing blood or recording vital signs?

Quarantine and stay-at-home mandates are compelling research organizations to increasingly adopt virtual technologies and procedures for gathering participant data. And Rowe says this movement was already trending prior to the pandemic. These days, data is often managed electronically. Diaries, questionnaires, weight scales, and consent forms can all be computed using computer and mobile devices. There are also calorie-counting apps and physical activity monitoring devices from which data can be extracted remotely.

Chaudhary says that studies initiated prior to the current pandemic, which were using in-person visits, have been switched to virtual visits if blood markers weren’t being measured. And if study participants are COVID-positive or have co-morbidities that keep them confined to their homes, phlebotomists are still making home visits with personal protective equipment kits, face shields, and masks while following other COVID-related protocols and social-distancing measures. Aside from these exceptions, she says that electronic case reporting and virtual trials in general are here to stay.

An increasingly virtual experience indicates that clinical research can be conducted without much hindrance, even while many communities are under lockdowns and people are leaving their home less often. Interested companies should be aware of the risks, though. “Be flexible with pass-through budget and understand that the more sites, the more protection, and [more] risk-managed a study becomes,” says Rowe. “Have a budget contingency in place to deal with having to change sites due to lockdowns.” Companies should also make sure that the contract research organizations and sites they work with have appropriate COVID-19 plans in place and contingencies in place to deal with potential related operational issues.

Is now the right time for clinical trials?

Clinical trials in the age of COVID-19

 is defined as “an approach to medical care that combines standard medicine with CAM (complementary and alternative medicine) practices that have shown through science to be safe and effective.”

 One area in which integrative medicine can be particularly useful is when specific nutraceuticals are used to help compensate for certain side effects caused by some prescription drugs. Due to space limitations, this article will address two common examples in detail and then list several others in a table.

Physicians often use statin medications as an important therapy in reducing and maintaining serum cholesterol levels in patients with hypercholesterolemia (i.e., high cholesterol levels). However, in addition to reducing cholesterol levels, statin medications also reduce the body’s production of coenzyme Q10 (CoQ10). In turn, this can lead to a myopathy marked by muscle pain in those patients prescribed a high statin dose.

In fact, the pharmaceutical suppliers of Lipitor (Pfizer)

 all state that significant decreases in circulating CoQ10 levels in patients treated with statins have been observed and that the clinical significance of a potential long-term, statin-induced deficiency of CoQ10 has not been established. This recognition is especially evident in the fact that Merck has even gone so far as to obtain two patents to combine CoQ10 with its statin drug.

Given the potential adverse effects of statin therapy, co-administration with CoQ10 makes a great deal of medical sense. 

 has established that pretreatment with CoQ10 reduced the toxic effects of statins and may protect cells from statin-induced injuries and alleviate their side effects. Likewise, animal research

 demonstrated that CoQ10 supplementation improved metabolic parameters, liver function, and mitochondrial respiration in rats with high doses of atorvastatin and a cholesterol-rich diet. Evidence from a review of human studies

 showed a benefit in symptoms of myalgia or improvement of serum levels of CoQ10 with supplementation of 30-200 mg daily of CoQ10, with no reported risks, in patients prescribed statins. In older athletes taking statins, 200 mg of CoQ10 daily improved muscle performance as measured by time to anaerobic threshold and leg strength. Many other measures of mitochondrial function also tended to improve.

 found that 200 mg of CoQ10 supplementation daily improved endothelial dysfunction in statin-treated type 2 diabetic patients, compared to placebo, possibly by altering local vascular oxidative stress.

Pharmaceutical treatments for depression are often associated with side effects. For example, common side effects of fluoxetine (e.g., Prozac) may include sexual dysfunction (decreased sex drive, erectile dysfunction, or difficulty having an orgasm).

Since saffron has shown aphrodisiac effects in some animal and human studies, a 4-week, randomized, double-blind, placebo-controlled study

 was conducted to assess the efficacy and tolerability of saffron stigma extract in treating fluoxetine-related sexual dysfunction. Thirty married male patients with major depressive disorder whose depressive symptoms had been stabilized on fluoxetine, and who had subjective complaints of sexual impairment, entered the study. The patients were randomly assigned to 30 mg/day of saffron stigma extract or placebo for 4 weeks. The International Index of Erectile Function scale was used to assess sexual function at baseline and weeks 2 and 4. Baseline characteristics, as well as baseline and final depressive symptoms scores, were similar between the two groups.

At the end of the study, saffron subjects saw significant improvements in sexual dysfunction (P = 0.009). By week 4, saffron supplementation resulted in significantly greater improvement in erectile function (P < 0.001), intercourse satisfaction (P = 0.001), and total sexual health scores (P < 0.001) compared to the placebo group. Nine patients (60%) in the saffron group and one patient (7%) in the placebo group achieved normal erectile function (score > 25 on erectile function domain) at the end of the study (P = 0.005). Frequency of side effects was similar between the two groups. In conclusion, saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction.

A similar randomized, double-blind, placebo-controlled study

 was conducted with 34 women with major depression who were stabilized on 40 mg/day of fluoxetine for a minimum of 6 weeks and who had experienced subjective feeling of sexual dysfunction. The patients were randomly assigned to saffron (30 mg/daily) or placebo for 4 weeks. Measurement was performed at baseline, week 2, and week 4 using the Female Sexual Function Index (FSFI).

At the end of the fourth week, patients in the saffron group had experienced significantly more improvement in total FSFI (p < 0.001), arousal (p = 0.028), lubrication (p = 0.035), and pain (p = 0.016) domains. Frequency of side effects was similar between the two groups. In conclusion, it seems saffron may safely and effectively improve some of the fluoxetine-induced sexual problems, including arousal, lubrication, and pain.

Other Medications and Nutraceutical Relationships

The following information comes from previous research that I published

Clearly, there are far more nutraceuticals that can be used to help compensate for certain side effects caused by other prescription drugs than can be addressed in the scope of this article. Nevertheless, the examples given—especially the relationship between statins and CoQ10—represent an integrative medicine approach to some common drugs and nutraceuticals.

Gene Bruno, MS, MHS, RH (AHG) possesses 42 years of dietary supplement industry experience. With a master’s degree in nutrition and a second master’s degree in herbal medicine, he has a proven track record of formulating innovative, evidence-based dietary supplements. Mr. Bruno currently serves as both the Vice President of Scientific and Regulatory Affairs at 

 and Professor of Nutraceutical Science at Huntington University of Health Sciences.

“Complementary and Alternative Medicine.” National Cancer Institute, National Institutes of Health. Updated November 24, 2020. Retrieved April 7, 2021. 

Ginter E. “Statins, coenzyme Q10 and diabetes type 2.” 

Lipitor® (atorvastatin calcium tablets) 10 mg, 20 mg, 40 mg and 80 mg atorvastatin. Lipid Metabolism Regulator. T.M. Pfizer Ireland Pharmaceuticals. Licensee: Pfizer Canada Inc. (Kirkland, QC, Canada). Date of Revision: May 29, 2013. Submission Control No: 163180. Page 7, Effect on Ubiquinone (CoQ10) Levels.

Zocor® simvastatin tablets, 5, 10, 20 and 40 mg. Merck Standard Lipid Metabolism Regulator. Licensee: Merck Canada Inc. (Kirkland, QC, Canada). Date of Revision: February 21, 2014. Submission Control No: 170366. Internal Filing May 6, 2014. Page 6, Endocrine and Metabolism.

Crestor® rosuvastatin calcium tablets, 5, 10, 20 and 40 mg. Lipid Metabolism Regulator. Licensee: AstraZeneca Canada Inc (Mississauga, ON, Canada). Date of Revision: April 28, 2010. Submission Control No: 130015. Page 5, Cardiovascular Co-enzyme Q10.

Patent No. US 4,929,437 and US 4,933,165. Patent date: January 18, 1989

Eghbal MA et al. “Efficiency of hepatocyte pretreatment with coenzyme Q10 against statin toxicity.” 

Jiménez-Santos MA et al. “Coenzyme Q10 supplementation improves metabolic parameters, liver function and mitochondrial respiration in rats with high doses of atorvastatin and a cholesterol-rich diet.” 

Littlefield N et al. “Statins' effect on plasma levels of coenzyme Q10 and improvement in myopathy with supplementation.” 

Journal of the American Association of Nurse Practitioners, 

Deichmann RE et al. “Impact of coenzyme Q-10 on parameters of cardiorespiratory fitness and muscle performance in older athletes taking statins.” 

Evidence shows that an integrative medicine approach pairing some common drugs and nutraceuticals makes sense.

Nutritional Outlook Vol. 24 No. 6