Greatest of care: The bar for studying infant and children’s supplements is high—and so are the challenges

Nutritional Outlook, Nutritional Outlook Vol. 24 No. 9, Volume 24, Issue 9

Even with all the obstacles involved in conducting research in this age demographic, companies continue to ensure they are investing in scientific research to back their immune-support ingredients for infants and children.

The pandemic changed everything in our lives, but especially the way we view our health. Immune concerns took center stage, and the dietary supplement and functional food industry experienced big bumps in sales for ingredients and finished products believed to address those concerns. But what did the heightened awareness of immunity mean for parents? Did the sales trend translate to infants’ and children’s products?

For many companies in the industry, that answer is a resounding “yes.”

According to Sam Michini, vice president of marketing and strategy, Deerland Probiotics & Enzymes (Kennesaw, GA), “The undeniable rise in cases of COVID in children and the fear in parents that their kids may contract it has driven sales of any and all immune products for kids through the roof. And this is never really a bad thing—all parents want their children to have sufficient immune strength.”

It’s also a “yes” from John Quilter, the vice president of global portfolio, proactive health, Kerry (Beloit, WI). He cites the numbers to back it up. A recent global consumer survey from Kerry found that immune support is the number one reason why parents purchase healthier foods and beverages and nutritional supplements.1

For example, he notes that in the 12 months leading up to the end of November 2020, sales of children’s multivitamins in the U.S. mainstream supplements market increased by 37.2% to $306 million.2 As Michini reminds us, “The largest-selling children’s supplement is the multivitamin, according to Nutrition Business Journal.

But it’s not just the multivitamin that is experiencing growth in the children’s market.

FrieslandCampina Ingredients (Amersfoort, The Netherlands) recently conducted a global insight study3 with the support of registered healthcare practitioners in the U.S., China, and the UK, which revealed that 70% of pediatricians have prescribed dietary supplements such as minerals, and pre- and probiotics, to their patients over the past year, according to Sophie Nicolas, the company’s marketing manager, early life nutrition.

The Pandemic: Just One Factor Pushing Immunity-Support Products

And it wasn’t just the pandemic that was responsible for a growing interest in immunity concerns from parents for their children.

Quilter advises that “demand for immune health products for kids is very high, and that this long predates the pandemic. As any parent knows, keeping children healthy means more days spent together as a family, and fewer school days lost.”

As Henna-Maria Kailanto, PhD, senior scientist, IFF Health (New York City), explains it, while the growth in an overall broad concern about children’s immunity grew even more during the pandemic, it actually reinforced the preexisting demand for children’s immunity products.

Nicolas says FrieslandCampina has certainly seen growing interest in immune health solutions for the child and infant demographic, noting “it’s natural for parents to want to protect the health of the ones they love most, and their concern will rise during times of greater risk.”

One of the things her company’s recent global consumer research study uncovered4 was that “in the U.S., 49% of parents of children aged 0-12 months are concerned about their infant’s immune health, making this one of their biggest priorities overall.”

But like Quilter and Kailanto, Nicolas sees the pandemic as being only partly responsible for the growing interest in immunity. “This is not only because of heightened interest in immune health as a result of the pandemic, but also because mums and dads have long been seeing immunity-related symptoms in their child’s first year of life,” she says.

She adds that “caregivers also have to contend with a huge variety of potential diseases and immune threats as children grow, including respiratory and digestive issues. So, no matter what is going on in the world, immunity will always be a priority.”

Michini raises another important point: “Adults who have felt or perceived success incorporating immune support supplements in their regimens are more easily encouraged to ensure their children follow suit as they believe in the value of immune support supplementation.”

Scientific Research in Children Presents Challenges

With the increased interest in children’s products for immunity comes an even greater responsibility to make sure that products are safe and do what they say they can do.

“Obviously when you’re marketing products for children [and] infants, your target audience is the concerned parent who wants the absolute best for their kids,” says Kerry’s Quilter, whose company makes Wellmune, a yeast beta-glucan for immune health. “That means that a demonstrable commitment to safety, scientific substantiation, openness, and transparency is of the utmost importance, even more than it is in products for adults.”

Quilter shares that Wellmune is supported by over a dozen published, peer-reviewed clinical studies, many of which have demonstrated benefits for kids specifically.

And while there are always challenges in conducting scientific research, somehow the challenges seem even greater when the research will be used as substantiation for the younger among us.

Safety Is Top of Mind

For Kyle Krause, product manager, functional fiber and carbohydrates, North America, Beneo Inc. (Parsippany, NJ), “Safety is of the utmost importance.”

According to Krause, “The safety and efficacy of Beneo’s prebiotic bioactive substances have been demonstrated for use in infants and small children.5” In fact, he adds that these ingredients are some of the most studied on the market, resulting in their being trusted by those companies who are formulating for infants and children.

Safety is one of the reasons why it is important to Beneo to work with trusted academic partners, says Krause, those “who can provide both a safe environment for study and a non-biased view of the scientific study findings, while pushing the science forward in the field of gut microbiota in this age group.” He notes, “These are experts in their field and astute at discovering the most nuanced reactions to food ingredients.”

The safety aspect is not lost on anyone. Morgane Maillard, marketing group manager, Lallemand Health Solutions (Mirabel, Canada), says, “Health and safety are big concerns when conducting clinical studies with infants and children, as these specific populations require higher standards.”

Consent, Compliance, and Other Challenges

One of the challenges of conducting scientific research for products intended to be used by children and infants is the necessity to obtain parents’ consent, says Maillard, “and then, to make sure there is good follow-through and good compliance during the length of the study.”

Conducting scientific research in the immune health category is always challenging, states Maillard, and is something she’s keen to talk about. “Researchers can choose to look at beneficial effects on general health, such as the reduction of incidence of common cold-like symptoms, or to check the enhancement of immune defenses by considering the levels of immune competence and mucosal immunity markers.”

According to John Deaton, PhD, vice president of science and technology, Deerland Probiotics & Enzymes, there are two main challenges unique to research in the infant/children population. Dosage form is the first.

He points out the need to confirm “that your product is in a safe and desirable delivery format to ensure there is no potential for choking. Depending on the target age group, traditional tablets or capsules may not be options.”

In Deerland’s clinical trials, Deaton has handled that issue by using highly stable ingredients— (the Deerland branded probiotic ingredient is Bacillus subtilis DE111)—which, says Deaton “has allowed us to use delivery formats like quick-dissolve stick-packs or gummies that may not be options for ingredients that are more susceptible to manufacture or storage stress. We’ve also utilized popular flavoring, like chocolate, to make dosing a desirable experience for children, and as such have seen almost perfect compliance.”

Deaton identifies “sampling” as the second unique challenge in infant and children’s research. Whereas in immunity-focused clinicals for adults it is customary to evaluate immune markers (e.g., pro-inflammatory cytokines) in the blood or saliva, he says, it is often not “feasible or possible to get the amount of blood or saliva necessary [with infants or children] to accurately make these measurements. Clinical trials in these populations often must be designed around other tests, including fecal microbiome analyses, and incidence and duration questionnaires.”

But even stool samples require special analysis considerations when it comes to infants and children. “Depending on what is being measured, it may be necessary to treat stool samples before analyzing to remove inhibitors,” states Deaton. “A healthy adult tends to have a stable and more established microbiome than children, in whom the microbiome is still developing. In these cases, it helps to look at microbiome diversity measurements and not just shifts in genera.”

IFF supplies several branded ingredients for children and immune health under its Howaru line, including Protect Baby, Protect Early Life, and Protect Kids, each featuring different probiotic strains. The company takes a number of steps to ensure safety when it comes to research for children, including following international Good Clinical Practice guidelines provided by the International Conference on Harmonization and ethical principles for medical research as identified by the World Medical Association’s Declaration of Helsinki policy statement, says Kailanto.

One of the challenges with children’s research is compliance, she points out—making sure infants and children take the probiotic as required in the study. “We take this into consideration and ensure that caregivers are given instructions on proper administration of the study product,” she says.

FrieslandCampina’s Nicolas finds that in the infant category, “one of the biggest overall challenges is finding enough participants for clinical intervention studies, which represent the highest standard of research.” While noting that more women are choosing to breastfeed—something that FrieslandCampina fully supports—her company’s challenge is to “ensure that, when breastfeeding is not an option, the nutrition available to infants is of the highest quality.”

To meet that objective, Nicolas says, “in order to support recruitment for our studies, we are therefore moving towards multicenter trials more often.”

The Elephant…

And perhaps among the biggest elephants in the children’s research room is when and how to use studies in other age populations.

Nicolas doesn’t shy away from that issue. “As with infants, research into the effects of nutritional solutions on children is still a growing field,” she says. “Children have a more varied diet than infants, which makes it more challenging to study the impact of specific health ingredients—they are a much smaller part of the complete nutritional picture.” She adds that therefore, in some cases, “we look into the possibility of extrapolating expected findings by translating scientific data from studies in other age categories. However, when health benefits are expected to differ in young children, we make sure to establish dedicated studies for that age category to confirm the health effects of our products.”

The quality of infant and young child formula is already high, so continuous improvement is a challenge, according to Nicolas. But, she says, FrieslandCampina has passion for that challenge. And excellent science, she adds, drives new thinking across the company’s product portfolio.

“When we study the potential immune health benefits of our ingredients, we ensure that every study group is of sufficient size to provide meaningful results. And we reinforce our own research with an extensive knowledge of and collaboration with the global academic community, including the world’s leading researchers in the field,” shares Nicolas.

New Studies Added to Scientific Literature

Even with all the challenges involved in conducting research in this age demographic, companies continue to ensure they are investing in scientific research to back their immune support ingredients for infants and children.

A recent IRB-approved, randomized, double-blind, placebo-controlled clinical trial on Deerland’s probiotic DE111 resulted in two published studies6,7 in late 2020 and early 2021 with good news results.

The first showed that daily intake of the probiotic strain B. subtilis DE111 was able to introduce subtle but positive changes in the gut microbiome profile in children aged 2-6 years old and attending daycare, without changing the overall microbiome equilibrium.6,7

The second published study from the trial suggested that daily consumption of 1 billion CFU of B. subtilis DE111 supported a healthy gastrointestinal tract with a reduced duration of vomiting, hard stools, and overall gastrointestinal discomfort. The study was conducted in young children attending daycare. Additionally, it showed the probiotic is well tolerated and safe to use in children 2-6 years old.8,9

A new study published in 2021 suggested that supplementation with the probiotic combination Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07—two branded probiotic strains found in IFF Health’s Howaru Protect Kids—can have a significant impact on a simulated viral immune response in blood cells collected from young children taking probiotics. The researchers suggested that further studies are needed to better understand the mechanism by which probiotics ameliorate symptoms in viral upper respiratory (and gastrointestinal) infections. Additionally, the study found that the probiotics product was safe and well tolerated.10,11

The study was a collaborative effort between IFF (formerly DuPont Nutrition & Biosciences) and the University of Wisconsin–Madison and was conducted in a population of 21 children (with two dropping out) over a 30-day time period.10,11

The Rosell Institute for Microbiome and Probiotics by Lallemand published a comprehensive review12 in June 2021 summarizing 28 clinical studies—with all but two covering the efficacy of Probiokid, Lallemand’s multistrain probiotic ingredient with Rosell-52 (Lactobacillus helveticus), Rosell-33 (Bifidobacterium infantis), Rosell-71 (Bifidobacterium bifidum), and fructooligosaccharides (FOS). Infants from birth through up to seven years old were included in the trials.13

Among the conclusions reached by the authors was this: 12 studies showed that the probiotic ingredient significantly increased the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unsolved diarrhea by 69%.12

The scientists further reported that in eight studies, the probiotic enhanced immune defenses—assessed by levels of various immune competence and mucosal immunity markers (six studies)—and reduced the incidence of common infections (two studies).12,13

The review also included safety data conducted on the three single strains separately.

Beneo expanded its chicory root fiber and rice starch ingredients portfolio in June 2020 with the addition of two new organic branded solutions: Orafti Organic and Remyline O AX DR (an organic waxy rice starch). According to Beneo, in a press release, “Consumers worldwide are increasingly seeking out organic products, with figures showing they have become more important to one in four consumers in the last year and many willing to pay a premium price for them.”14

Remyline O AX DR was “the first of its kind to be brought to market, opening up new possibilities for product development,” Beneo says14. Steven Gumeny, product manager, rice ingredients and functional proteins, Beneo, says that “rice is not only clean and natural; it is also incredibly functional. Research shows that parents appreciate seeing rice on the label as it has a natural perception15…and in addition, rice is easy to digest…”

Beneo also had good news on the science front. In a press release16 from April 2021, Beneo announced that a published study17 demonstrated that the prebiotic fortification of infant formula milk with Beneo’s oligofructose-enriched inulin was shown to reduce the duration of infections in the first year of a baby’s life.

The infant formula in the study was either enhanced with 0.8 g/100 ml of Beneo’s Orafti Synergy1, a chicory root–derived prebiotic, or an unsupplemented control formula. The findings demonstrated that the babies who consumed the Orafti Synergy1 formula had significantly shorter infection episodes compared to the control group.16,17

This study is part of the EARNEST (EARly Nutrition programming-long term follow up of Efficacy and Safety Trials) project, an EU-funded integrated initiative. This is the third study using the same dosage of Orafti Synergy1 showing safety, good tolerance, and health benefits, but it is the first long-duration trial to show these results, the company adds.16

FrieslandCampina’s Nicolas says, “Nourishing the gut microbiota with oligosaccharides can support the infant immune system.” She references a recent study18 that adds to the body of literature showing that “oligosaccharides such as galacto-oligosaccharides (GOS) and human milk oligosaccharides (HMOs, which include variants such as 2’-FL, LNT, and 3-FL) have been shown to stimulate growth of Bifidobacteria by serving as a substrate.”19,20,21

“This enables the outnumbering of pathogenic bacteria through competitive advantage,” says Nicolas—a result demonstrated in another recent study.22

These two new studies are important, according to Nicolas, because “these underlying mechanisms of action have been connected with specific infant health outcomes such as showing a reduced incidence of infections in babies nourished with formula containing GOS.”

FrieslandCampina’s Vivinal GOS ingredient has been on the market for over two decades and comes supported by over 55 clinical studies, says Nicolas. The company also touts its Aequival range of human milk oligosaccharides (HMOs). “A lot of research is in progress investigating how gut healthy ingredients like HMOs and GOS can support infant immunity and more,” she says.

Room to Grow for Children’s Immune Products?

“At a time when consumers are more interested than ever in taking a preventative approach towards their own health and their children’s health…it makes sense that the infant immune health category will continue to grow over time, meeting the needs of these consumers even after the pandemic has passed,” says Nicolas.

Deerland’s Michini sees children’s immune support supplements becoming more of a mainstay in parents’ care regimens. “The pandemic has taught parents—and young adults who will become parents—about how vulnerable even healthy people can be to a sudden epidemic or pandemic.”

And just as the pandemic made us more comfortable with masks, hand hygiene, and other social behaviors driven by the crisis, Michini thinks that “consuming dietary supplements and functional foods/beverages that stimulate appropriate and strong immune functionality is going to become as routine for children as their multivitamins.”

Kerry’s Quilter advises, “The trend to watch is the growing consumer need for scientific substantiation, and the ingredients to watch are those that meet it. However,” he adds, “it’s not enough to rely on scientific evidence supporting a broad category; you have to be able to demonstrate the benefits of the specific ingredient.”

IFF Health’s Kailanto sees two trends that will make a difference in category growth: combination products and enticing kids to consume new products, taste, and texture.

“Overall,” she says, “We see early-life immune health as a very promising segment since it is the first years of life that offer a window of opportunity to support immune system development and programming for future health.”

Beneo’s Krause agrees, stating that nutrition in early life is crucial for development, with implications throughout one’s lifespan. “The focus on both infant and children’s nutrition has a very promising future,” he says, adding that “research available on clinically proven ingredients that can contribute to infant and children’s nutrition is key.”

References

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  14. Press release. “Beneo Expands Portfolio with New Organic Ingredients.” www.globenewswire.com. Posted June 17, 2020.
  15. Haystack Consulting consumer survey. “Rice Is Recognized as a ‘Cupboard Ingredient’ that is ‘Healthy’ and ‘Easy to Digest.’” 2018.
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