At IFT FIRST in Chicago in July, a panel of food scientists discussed recent technological innovations related to improving the bioavailability of nutrients in foods.

The discussion included: Paul Moughan, professor and Riddet Institute fellow laureate at Massey University; Ray Matulka, PhD, director of toxicology and executive vice president at Burdock Group Consultants; Taylor Wallace, PhD, CFS, FACN, principal and CEO at the Think Healthy Group and adjunct professor of Nutrition at George Mason University; and Dr. Lingyun Chen, professor at the University of Alberta.

What is a Bioactive?

Matulka brought to the discussion some history of research behind plant bioactives, which he defines as a class of phytochemicals which are considered by researchers to be “nutritive” in nature when consumed at higher levels than what one typically gets in the diet, or when these phytochemicals are modified for increased absorption. Some non-essential nutrient examples that he gave included flavonoids, resveratrol, certain insoluble fibers that don’t meet FDA’s definition of a dietary fiber, and others. 

“Bioactive is a term that has been around for many years,” Matulka said. “Nutrients are known to be substances that promote growth and provide energy […] because the food industry is reliant upon the FDA and their definitions, FDA’s definition is that nutrients are ingredients required in accordance with a specific nutrients table that’s set by the Food, Drug and Cosmetics Act […] or are defined as essential for infants by the Food and Nutrition Board of the Institute of Medicine […].”

The term bioactive doesn’t have a clear-cut definition, however, “there are components of the diet that provide a benefit above and beyond essential nutrition,” Matulka said. With a knowledge gap in the safety and efficacy of these bioactives when consumed at high or modified levels, he noted that a comprehensive array of studies are needed to expand the concept of “nutritive value” in a way that can include bioactives. 

Matulka hopes the industry will push regulatory bodies to incorporate research on non-nutrient bioactive compounds into their purview, as structure-function claims for conventional foods must be derived from nutrients only by current regulations. The rules surrounding claims for either nutrients or bioactives will likely remain compartmentalized, he said, mainly because there are disease states associated with not getting enough of a nutrient, which is not the case for any given bioactive.

Gold standard randomized, controlled human clinical trials are needed to drive bioactive ingredients forward into the mainstream. Matulka noted, however, that the burden of proof for bioactive ingredients can be a relatively high hurdle, as bioactive substances often have a complex effect on health by inducing many small changes, which is difficult to quantify.

“I believe that there are regulatory bodies like the European Union and the European Food Safety Authority open to allowing for a lot more in terms of bioavailability and bioactive claims for ingredients such as polyphenols and others,” Matulka said. “These agencies have gotten a lot more strict over the past few years, but at least they have a framework to allow for the use of some claims on labels. Perhaps [U.S. regulators] could look at that framework and see if parts of that model could be implemented, on the food side. The science is there to show that bioactives have a benefit beyond just essential nutrition; it becomes a matter of developing the guidelines to establish claims for consumers.”

Flavan-3-ols: The First-Ever DRI for a Bioactive

Wallace, a nutrition researcher specializing in flavonoids, was involved in synthesizing decades of data from peer-reviewed human studies to achieve the first ever daily recommended intake for a non-nutrient bioactive, flavan-3-ols (a subclass of flavonoids commonly found in tea and berries), thanks to supporting evidence for their role in cardiometabolic health. Flavan-3-ols are likely beneficial due to a combination of antioxidant, inflammatory-modulating, anti-mutagenic, and anti-carcinogenic properties as well as their modulating effects on cellular enzymes, according to Wallace.

“This is a project that’s been going on for about two years now,” he said. “The guideline development process for flavan-3-ols is very unique but somewhat similar to how we develop recommendations and guidelines for other nutrients, and it’s particularly similar to the process we had for dietary fiber. The framework for establishing a recommendation includes what intakes of flavan-3-ols currently look like in the U.S., then evaluating the safety, quantifying a causal relationship, and, finally, translating the evidence into the intake statement which is currently in its draft form and under peer review.”

According to Wallace, the guideline development process incorporated data from over 150 clinical trials on flavan-3-ols, incorporating safety ahead of clinical efficacy. More specifically, the analysis included an initial 157 (48 high-quality) randomized, controlled trials on cardiometabolic risk factors, meta-analyses on the cardiometabolic benefits with dose consistency, the EFSA Panel on Dietetic Products, Nutrition, and Allergies’ opinion on authorizing a health claim for cocoa flavanols, and the COSMOs trial, which was published earlier this year.

“We thought flavan-3-ols had the most evidence to date of the bioactives. The Academies felt it was appropriate to move forward with a clinical guideline and intake recommendation if possible,” Wallace said.

To inform the guidance development process, the team hired an independent panel of experts at Tufts University in order to provide a systematic review of the quality of the evidence via what is known as the GRADE Evidence to Decision Framework.

To some surprise, Wallace said that the evaluation by the independent panel of the evidence was standard across the board. Historically, for the flavonoid class of bioactives, the biggest hurdle to overcome in the development of daily recommended intakes (DRIs) was establishing population-based models of intake. “The National Academies attempted to publish DRIs for polyphenols in the late 1990s, but determined there was not an ability to do so because the intake quantification wasn’t there. Since then, we’ve had the development of the USDA flavonoid database, and we have a better idea of what intakes look like in the U.S.”

“This is the first time this has been done in North America. It’s important to have a DRI-like process for bioactives,” Wallace said. He pointed to a proposed definition of bioactives by the National Institutes of Health, which reads that bioactives are “constituents in foods or dietary supplements other than those needed to meet basic human needs, which are responsible for changes in health status.”

Bioavailability in Plant-Based Alternatives

Bioavailability is sure to become a major point of attention among those formulating plant-based meat alternatives, according to Dr. Lingyun Chen, professor at the University of Alberta. Some of her most recent research has looked at food formulation methodologies that can be used in order to ensure that plant-based meat and dairy alternatives can be fortified with nutrients missing from the plant-based diet while ensuring that they are absorbed similarly to the vitamins and minerals found organically in meat and dairy.

“In addition to taste, texture, and color, nutritive value remains a major challenge for plant-based meat,” Chen said. “In terms of nutritive value, some recent research has found that plant-based protein products are good in dietary fiber, linoleic acid, alpha-linoleic acid, vitamin E, and folate. However, they are normally very low in vitamin B12 which can only be found in animal sources. The iron, zinc, and calcium added to these products also have very low bioavailability.”

However, she and her team found that plant-based proteins can be ideal for nutraceutical delivery, given that the right dosage technologies are used. For instance, gels and emulsions can be used as a network to encapsulate all water-soluble nutrients, allowing for optimal delivery through a variety of plant-based food products. Use of these food technologies has yet to hit mainstream plant-based meat and dairy alternatives.

Among other research, Chen and her team developed a soy protein gelation technology which effectively contained microcapsules of vitamin B12. It was substantiated in both in vivo models of B12 deficiency and in ex vivo models of the human intestinal environment to sustainably release B12 from the soy protein base and the microcapsules were able to be modified to control the release speed to ensure improvements to potential bioavailability. In another study, Chen noted that researchers were able to bind minerals to plant protein peptides, increasing the bioavailability of minerals like iron, calcium, and zinc exponentially compared to the control, which was these minerals at the same dosage in a free form.

“We can develop encapsulation systems that attach to nutraceuticals and control their release and absorption. There are several other technologies that have also attracted attention. For example, in oat milk, all of the fiber is lost during processing, but we can add it to the oat cell walls. Our research demonstrates that when we have plant-based emulsions, if we can control the size of the microcapsules we can significantly improve the availability of many different nutrients. 3D printing is another technology where you can have a protein matrix and add different combinations of nutraceuticals, while also providing unique textures to foods,” Chen said. “Isolating plant proteins, rather than using protein flours or protein concentrates which have more nutritive value, is something we really need to reconsider as a food industry.”

Time to Scrap PDCAAS? 

There is a new methodology to look at protein quality set to overtake PDCAAS (protein digestibility corrected amino acid score) which will become more mainstream and important given the advent of plant-based proteins in the mainstream, according to Paul Moughan, professor and Riddet Institute fellow laureate at Massey University.

PDCAAS was brought into the forefront as a protein quality evaluation method in 1991 by the Food and Agricultural Organization (FAO) of the United Nations, and it became an official standard in 1993. However, in 2013, FAO first proposed shifting its preference to the Digestible Indispensable Amino Acid Score (DIAAS).

PDCAAS is determined through comparing the amount of essential amino acids in food to a scoring pattern based on the dietary requirements of a two- to five-year-old child to determine the most limiting amino acid, and samples are taken using the feces of a mouse model. The greatest score a protein can achieve is 1.0.

On the contrary, the DIAAS model takes a look at digestible amino acid contents in food, to the same amino acid in a reference pattern taken from age-specific amino acid requirements, and samples are taken from pigs, a more favorable animal model due to the fact that pigs have more similarities to humans than mice. DIAAS scores are represented by a percentage value.

Because DIASS does not truncate scores to a maximum value, proponents consider it to be a more reliable measure of protein quality, according to Moughan. Further, amino acids are less likely to be absorbed after passing through the ileum—in the DIAAS model, amino acids are taken directly from the ileum for this reason, offering a more accurate representation of amino acid absorption.

“People confuse bioavailability and digestibility, and they don’t realize that just because something is digested it’s not necessarily utilized,” Moughan noted. “Amino acids are taken up from the gut into the bloodstream and can only be used for protein synthesis—whether or not that happens has a lot to do with other aspects of the diet, and the characteristics of the person consuming the protein. The utilization of amino acids will always be much lower than the amount that is bioavailable.”

With a mass of health- and sustainability-minded individuals gravitating toward sustainable food production and plant-based proteins, “we need to pay a lot more attention to combinations of protein sources,” Moughan said.

“We need to look at the complementarity between different proteins to provide more wholesome diets, and think more about amino acid bioavailability and supply […]. The industry needs to recognize that it’s the individual amino acids that are critically important, and we generally need to give more attention to describing the bioavailable amounts of key amino acids like leucine and cysteine. Unlike PDCAAS, DIAAS shows how good a protein is after it’s been consumed in a given form […] We need to better define not just the nutrient content but the bioavailable amounts of key nutrients, which is often not done in foods.”