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Child supplement doses present unique challenges.
Child supplement doses present unique challenges.
While the majority of today’s dietary supplements target adult use, more parents are turning to natural products and dietary supplements for their children’s health and wellness.1-3 More than 30% of American children under the age of 18 take dietary supplements, most commonly as multivitamins and minerals, according to a 2007 data analysis of the 1999–2002 National Health and Nutrition Examination Survey. Supplements usage was highest in children 4- to 8-years-old and lowest among infants and teens (ages 14 to 18).3 A similar percentage (33%) of parents surveyed in a study published in the Journal of Pediatric Health Care indicated that they used complementary and alternative medicine with their children within the past year, with vitamins and botanicals most commonly used.2 Also of note, use of supplements for children seems to be higher in certain groups, such as in Hispanic/Latino populations.1,4
The demand for children’s supplements is there, but as any dietary supplement marketer knows, formulating and manufacturing dietary supplements for children entails a number of challenges. We’ll discuss a few of those challenges ahead.
First off, the dosage form of a dietary supplement will differ depending on the age of child the supplement is meant for. Young children often can’t swallow capsules or tablets, for instance, so these dosage forms should usually be avoided. However, going with an alternative dosage form can add additional expense and challenges to manufacturing, introducing issues with solubility, storage, shelf life, and more.5
Adding to the challenges of an alternative delivery system, children also have well-developed senses of taste and smell, and therefore liquid, glycerite/syrup, tea, gummies, gel, powder, or dissolvable forms may still not go over well if the product has an unpleasant taste. Bitterness, for instance, tends to be especially unpleasing to children.6 Also challenging is that the sense of taste continues to develop and change throughout childhood. Therefore, developing flavors that are palatable for children across the board is nearly impossible.
Well, if taste is paramount, why shouldn’t a marketer then create the most delicious dietary supplement that it can? Therein lies a delicate balance. If children find a dietary supplement tooappealing, there are always concerns that they may overexpose themselves to the supplement-i.e., gobble it up like candy. (Of course, child-resistant packaging, warning statements on labels such as “keep away from children,” and specific dosing information on the label, can help mitigate such dangers.7)
Next is the often difficult task of determining the proper suggested dose or serving size of a supplement for children. In this area, vitamins and minerals have some advantage in that the Food and Nutrition Board at the Institute of Medicine (IOM) has recommended requirements for children across the developmental span.8,9 (Interestingly, in the case of many nutrients, data on children was not available and thus the IOM extrapolated data from adult recommendations using methods based on indices such as reference body weight or energy intake/expenditure.10)
But not all nutrient doses are so clear-cut when it comes to children, and those formulating dietary supplements containing botanicals or other ingredients without established requirements face more challenge in determining recommendations.
Children have been given botanical remedies for millennia in various cultures. Even today, a large percentage of the world’s population (adults and children) use traditional herbal remedies. Dosing regimens for fresh plants have been determined mainly by trial and error, often over long periods of time.11
Rather than fresh herbs, in today’s modern market, dietary supplements take on many different botanical forms-novel extracts, dried teas, juices, etc. Each contain various parts of the plant, are grown in various regions, and are processed in unique ways, making it difficult to compare products with regard to safety and efficacy-not only for children but for adults, too.
The complexity of botanical dosing issues was illustrated in an article about a study funded by the National Institutes of Health (NIH) on Echinacea use in children.12 Despite the many studies that had been previously performed using Echinacea, and Echinacea’s long history of traditional use, the biggest hurdles in designing the study were trying to determine the best herbal preparation to employ, the dosage scheme, and the duration of the study.
Interestingly, published research studies are often inadequate in carefully describing the supplement/drug test article and/or dose preparation that was used in the study so that it can be reproduced.13
From the modern study of developmental pharmacology, we know that children should not be considered merely “small adults” in terms of how to dose compounds. Formulas such as Young’s Rule, Clark’s Rule, or others have been used to calculate medication doses for children (See table 1, the second photo attached to this article).14 These formulas have also been used by practitioners to dose botanical ingredients to children.
Such formulas assume a predictable, linear dosing relationship using either an individual’s weight or age. Yet human development is not linear, and the ability to absorb, distribute, metabolize, and excrete compounds changes in various-and sometimes conflicting-ways as a child grows. For example, the pH of the stomach and gastric emptying time change during development, as does biliary function and microflora composition-all of which affect overall absorption. The efficiency of liver enzymes and kidney function matures throughout childhood, affecting metabolism and excretion of compounds. Emerging research on the interaction between certain compounds and cellular receptors suggests that these relationships also change throughout development.
As is obvious, the complex changes that happen during development don’t lend themselves to a clean linear solution for determining doses/serving sizes of supplements for children as compared to those for adults.14,15
Interestingly, the rising prevalence of obesity among children in the United States adds to the dosing conundrum, as body composition differences affect the volume of distribution of compounds.16,17 Currently, because there can be so much variation in weight within a given age group, weight-based dosing schemes, as opposed to age-based dosing schemes, are preferred when more specific information about pediatric dosing is unavailable.
Clinical studies currently provide the most specific answers about proper dosing strategies for substances intended for use in children. Yet even in the pharmaceutical industry, many of the drugs intended for use in children have not been adequately studied in children and/or don’t have FDA approval for use in children. Thus, in many cases, drug prescription for children is considered “off-label prescribing” and is done by physicians using some degree of trial and error (often by extrapolating from adult doses), combined with best clinical judgment that the medicine will be safe and effective for the child.18,19
Not that FDA doesn’t want to see improvements in terms of studying and determining precise dosages for children. In fact, regulators have made strong efforts to lay down guidelines and encourage pharmaceutical studies done in children. Some examples include the 1979 FDA regulation that spelled out requirements for pediatric labeling information on pharmaceutical package inserts. The FDA Modernization Act of 1997 offered pharmaceutical companies six additional months of “drug exclusivity” (financial incentive) for studying their medications in children. The Pediatric Research Equity Act gave FDA the ability to require that studies on a new drug be done in children if the drug is deemed likely to be used in a substantial number of pediatric patients.
FDA’s Best Pharmaceuticals for Children Act (BPCA) renewed the 1997 pediatric incentive program and provided mechanisms for studying both on- and off-patent drugs in children. Under the Act, NIH is required to identify drugs of highest priority for study in pediatric populations every three years. Also under the Act, an Office of Pediatric Therapeutics was created to coordinate pediatric-related FDA activities. Furthermore, in 2010, the National Institute of Child Health and Human Development announced support and dedicated funding for its initiative, the Pediatric Trials Network (PTN). The network is a groundbreaking alliance of clinical research sites that will provide an infrastructure for pediatric clinical trials, to support the goals of BPCA.
These initiatives have led to a large increase in the number of pediatric drug safety and efficacy studies, and the numbers will continue to grow. Results of such studies have shown that to be safe and efficacious, some drugs require higher or lower doses in various age groups than initially expected. The body’s ability to distribute or eliminate certain compounds was also different in children than what had been previously assumed. Furthermore, some studies showed that some drugs were only efficacious in children above a particular age.18 Overall, it is clear that our ability to predict the effects and the optimal dose at which a compound will work in a child’s body leaves something to be desired, and clinical studies provide the best conclusive answers.
Yet, as there is never an easy answer, clinical trials in children also bring many unique challenges, including ethical dilemmas. Children require extra protection in research studies, as they are less likely to be able to defend their interests and/or express their needs. Some additional difficulties in conducting these trials include how to properly obtain consent for study participation; parent-guardian objections to study protocols; developing dosing schedules that can reasonably be followed; obtaining adequate amounts of body fluids for pharmacokinetic/pharmacodynamic studies; and determining dosage forms, especially if the trial will involve various age groups of children and/or will last long enough that children will grow throughout the trial.20,21
Luckily, strides have been made in establishing guidelines for the ethical conduct of clinical research involving children, coming from groups such as the American Academy of Pediatrics, the IOM, the International Conference on Harmonisation, and the U.S. Department of Health & Human Services.22,23,19
And, while much of this discussion has focused on drug research in children, the number of clinical studies looking at how dietary supplements can promote health has increased rapidly in recent years, and many studies have been performed in children as well. But, like for drugs, there is still an enormous amount of room for research growth in this area.
In summary, developing dietary supplements for children involves many unique challenges for manufacturers. Supplement companies targeting children should well understand the complexities of making products for this age group as related to formulation, dosing, palatability, and/or labeling. Specialized consultants can be sought to assist in developing the safest, most efficacious, and tolerable products. These consultants may include flavor consultants, regulatory consultants, and naturopathic physicians, who are uniquely qualified to help with formulations due to their studies in natural pediatric medicine, botanical medicine, pharmacology, and more.
As more parents look to the dietary supplements industry for products to support their children’s health and well-being, the ultimate goal continues to be finding the safest and most efficacious supplements.