KANSAS CITY — Unlocking the science behind how molecules found in plants and fungi are bioactive within the human body could impact the food industry. With the possibility of recommendations to increase intake of bioactive ingredients as health benefits are identified, attention is being directed to bioactive ingredients sourced from cocoa flavanols, tea, turmeric and hemp.

The National Institutes of Health defines dietary bioactives as “constituents in foods or dietary supplements, other than those needed to meet basic needs, which are responsible for changes in health status.”

A bioactives coalition formed in July to advance education and advocacy of science-backed bioactive compounds among food and health industries, consumers, and policymakers. The coalition will facilitate interactions among food and health system leaders who want to incorporate bioactive compounds into US dietary guidelines. Another aim will be to provide education on the scientific evidence, advancements in research and discovery, and perspectives to inform bioactive use and regulation in functional food, beverage and supplements.

One board member, Taylor C. Wallace, PhD, principal and chief executive officer of the Think Healthy Group, was the co-author for the first North American guideline and intake recommendation for flavan-3-ols. The recommendations along with data on flavan-3-ols and cardiometabolic health were published in the November 2022 issue of Advances in Nutrition.

Increasing consumption of dietary flavan-3-ols has been shown to help improve blood pressure, cholesterol concentrations and blood sugar, according to the recommendation. The recommendation was backed up by 157 randomized controlled trials and 15 cohort studies that previously were reviewed in a published systematic review and meta-analysis.

“Among the general adult population, we suggest increasing consumption of nutrient-dense foods rich in flavan-3-ols and low (or absent) in added sugars, including but not limited to tea, apples, berries and cocoa,” the researchers said. “Based on moderate quality research, consumption of 400 to 600 mg a day of flavan-3-ols can reduce risk associated with cardiovascular disease and diabetes. Increasing consumption of dietary flavan-3-ols may help improve blood pressure, cholesterol concentrations.”

The guidelines recommend consuming flavan-3-ols in food, not dietary supplements, to achieve 400 to 600 mg per day.

“The potential risks of increasing flavan-3-ol intake through supplementation are of concern and warrant elaboration,” the researchers said. “Concentrated green tea extracts and purified catechins, including the well-known epigallocatechin gallate (EGCG), have been implicated in both benefits and harms from green tea. Liver injury and gastrointestinal distress are the most widely reported adverse effects associated with flavan-3-ol consumption, mainly arising from supplementation with concentrated green tea extracts in a fasted state.”

Dr. Wallace spoke at the IFT FIRST, the Institute of Food Technologists’ annual meeting and food exposition held in Chicago in July. Tea is the main driver of flavan-3-ol intake in the United States, he said, adding 2017-18 NHANES (National Health and Nutrition Examination Survey) data show flavan-3-ols are consumed more highly among Asians, Caucasians, women and consumers with higher incomes. Apples, berries, cocoa and cinnamon also contain flavan-3-ols. Their health-promoting properties likely are due to a synergistic combination of their antioxidant, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties, Dr. Wallace said.

The recommendation of 400 to 600 mg a day is higher than a European Food Safety Authority health claim of 200 mg per day of cocoa flavanols issued in 2012 after an application from Zurich-based Barry Callebaut. An EFSA panel concluded, “Cocoa flavanols help maintain endothelium-dependent vasodilation, which contributes to normal blood flow.” To obtain the claimed effect, 200 mg of cocoa flavanols should be consumed daily, according to the panel. The amount could be provided by 2.5 grams of high-flavanol cocoa powder or 10 grams of high-flavanol dark chocolate, both of which can be consumed in the context of a balanced diet.

Before the health claim was approved, Barry Callebaut carried out over 20 human clinical studies examining various impacts of cocoa flavanols on the human body. The company through its Acticoa process was able to maintain up to 80% of the cocoa flavanols in chocolate production, which would be destroyed for the most part during the conventional chocolate-making process, according to Barry Callebaut.

Barry Callebaut submitted a petition Nov. 21, 2018, to the US Food and Drug Administration for a qualified health claim stating “supported but inconclusive evidence” suggests consuming at least 200 mg of cocoa flavanols daily may reduce the risk of cardiovascular disease. The FDA earlier this year said it does not plan to object to the use of certain qualified health claims about consuming cocoa flavanols in high flavanol cocoa powder and a reduced risk of cardiovascular disease. The FDA, however, determined “very limited credible scientific evidence” exists for the reduced risk, which in turn will limit the wording in the qualified health claims.

What do consumers know?

Brightseed, San Francisco, a bioscience and artificial intelligence (AI) company, was active in forming the bioactives coalition. The company in 2022 surveyed 2,800 US adults about their awareness and understanding of bioactives, said Alina P. Slotnik, vice president.

“Over 50% of consumers said they were interested in increasing their intake of bioactives, and 27% of respondents, representing more than a quarter of US adults, fell into a category of consumers we call ‘bioactivists,’” she said. “Bioactivists are a category of consumers that are motivated by health as the primary driver of their purchasing decisions. They want tangible proof that something works, and they want to understand why. What’s more, 67% believe their favorite brands should communicate about the bioactive content in their products. We’re eager to continue to follow the trajectory of health-savvy consumers who are not only examining labels, but also following the science behind functional ingredients.”

Bioactives may be found in plants, fungi and bacteria, she said. Each bioactive has a unique potential to support specific areas of health. Brightseed used its Forager AI-powered platform to identify two bioactive compounds with gut barrier benefits in multiple plant sources: N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT).

“Science knew these compounds existed within the plant kingdom, but their impact on human health was unknown,” Ms. Slotnik said. “Forager was able to connect NCT and NFT as potent agonists to the HNF4a receptor in a matter of months, opening up extraordinary new possibilities for understanding their full potential on key metabolic pathways. Clinical investigations are ongoing, and thanks to Forager, hemp hulls were identified as the richest known source of these two bioactives.”

Preclinical studies conducted by Brightseed showed the potential of the two bioactives to support gut barrier function. The results were published this year in the Journal of Food Bioactives.

“We are thrilled by this publication as it is an exciting addition to the already growing body of research on the potential health benefits of bioactives,” Ms. Slotnik said. “And to bring these potential health benefits to consumers, we developed a proprietary process to transform upcycled hemp hulls into a dietary fiber ingredient — Brightseed Bio Gut Fiber — that has a high concentration of NCT and NFT.”

Potential applications for Bio Gut Fiber are bars, crackers, baked foods, cereal, granola, and nutritional and powdered beverages, she said.

“From brownies and croissants to muffins and breakfast bars, there is ample opportunity for Bio Gut Fiber to be formulated into a functional baked food,” she said.

Bio Gut Fiber is an insoluble fiber, which provides greater flexibility in applications when compared to soluble fiber, Ms. Slotnik said.

“Bio Gut Fiber easily incorporates into flours and dry powders, doesn’t absorb oil or water, and is resistant to heat, pH changes, and enzymatic degradation,” she said. “Bio Gut Fiber is a whole food ingredient, made only from hemp hulls and has a light, nutty aroma.”

Earlier this year Chicago-based ADM and Brightseed formed a global joint partnership to develop evidence-based functional symbiotic products that target microbiome optimization. ADM is leveraging Brightseed’s AI platform Forager to decipher the molecular interactions between dietary plants and gut microbes.

Turning to turmeric

Turmeric also is known for bioactive activity. NutriOriginal, Fairfield, NJ, this year introduced TurmiMax Bio, a 95% standardized turmeric extract with exceptional bioavailability, enhanced absorption, and full dispersion and solubility in water, according to the company. Potential applications include liquid supplements, functional beverages, shots, gummies and food.

NutriOriginal collaborated with Star-Hi Herbs, Bangladore, India, to create the ingredient through a patented blend of naturally occurring curcuminoids and a proprietary OptiBio assurance process.

“Our goal was to go beyond delivering a standard 95% curcuminoid extract,” said H.M. Firoz Hussain, co-founder and managing director of Star-Hi Herbs. “Through the proprietary OptiBio Assurance process matrix, we’ve entered a new frontier in bioavailability that optimizes the potential of traditional turmeric.”

NutriOriginal will showcase TurmiMax Bio at SupplySide West in Las Vegas Oct. 25-26.

Curcumin is a bioactive compound found in turmeric, according to Glanbia Nutritionals, which has a US office in Chicago. The company encapsulates curcuminoids with B-cyclodextrin to improve solubility and stability in its CuroWhite ingredient. The encapsulation process gives CuroWhite a milder taste and smell compared to standard curcumin. Potential applications include bars, powder drink mixes, ready-to-drink beverages, gummies, gels, tablets and capsules.

For another bioactive ingredient, Glanbia’s PepForm tryptophan binds free-form amino acids or bioactive compounds to peptides isolated from fresh sweet whey using fractionation and separation technologies. Melatonin, which governs the body’s circadian rhythm to help regulate sleep cycles, is synthesized from tryptophan, an essential dietary amino acid.

More research coming

Millions of bioactives found in plants and fungi are still to be discovered, according to Ayana Bio, Boston. Since the molecules are trapped inside plants and fungi, they are expensive and inefficient to extract, but Ayana Bio has opened a laboratory in Boston’s seaport district to formulate plant cell-cultivated production systems to create ingredients without growing plants in the ground. Ayana Bio has partnered with Ginkgo Bioworks, which has a synthetic biology platform, to develop bioactives at scale using cell-culture technologies.

Nuritas, a biotechnology company based in Dublin, uses artificial intelligence (AI) to discover bioactive peptides. The company plans to build its North American headquarters in Connecticut near Yale University in New Haven.

Nuritas has created a peptide knowledge base using its proprietary AI and genomics platform that analyzes billions of hidden and untapped peptides in plants and natural food sources to predict and identify how they impact specific health areas, molecular pathways or receptors. The peptides are validated in a laboratory and tested clinically. They are scaled and patented before Nuritas takes them into the market. The branded molecules may be integrated into consumer products for topical or oral use.