In this randomized, double-blind controlled study, we aimed to assess the glycemic and insulinemic responses to three main types of formula. We found no differences in the glycemic index between the standard (cow's milk protein-based containing lactose), the lactose-free, and the soy protein-based formula. However, peak blood glucose levels were significantly higher after consumption of a soy protein-based formula.
Epidemiological evidence suggests that a diet based on low glycemic carbohydrates has many benefits, especially in an era when obesity is becoming a global epidemic [8, 9, 19]. Several studies have examined and demonstrated the effect of certain carbohydrates and amino acids on post-prandial glycemia and insulinemia [6, 20–25], but there is little information on the differences in metabolic response to various infant formulas. Wright et al. [17] compared glycemic and insulinemic responses to breast milk and standard infant formula among 10 healthy breastfeeding mothers, and found no differences between them. In that part of their study, similarly to ours, each volunteer consumed both her own breast milk and infant formula. In the second part of their study, 11 formulas that differed in carbohydrate and protein composition were tested among 10 healthy young adult volunteers, and a wide range of responses was demonstrated. It is well known that the metabolic response differs among people, and it is possible that this also affected the differences observed by Wright et al. Our current double-blind study, which included almost twice as many volunteers, compared the glycemic and insulinemic responses to different kinds of infant formula, but did so while eliminating the variability in metabolic responses between different individuals, since each subject served as his/her own control.
To the best of our knowledge, our study is the first to compare glycemia and insulinemia as the result of consuming standard formula with formulas containing carbohydrate or protein substitutes in healthy adults. Our findings might be clinically relevant because high postprandial glucose levels, especially during the growth period and metabolic programming in infancy, might have long-term adverse effects. The present study showed that standard cow's milk formula, lactose-free formula, and soy protein based-formula had similar glycemic index despite their different compositions. However, our findings demonstrated that the consumption of a soy protein-based formula resulted in a significantly higher increase in postprandial peak glucose levels. The implications of similar glycemic indexes but different peak glucose levels have yet to be explored, but they may indicate rapid changes in blood glucose concentrations following consumption of soy protein-based formula. These fluctuations in glucose levels may increase hunger levels, cause rebound hypoglycemia, and impair the body's ability to maintain stable blood glucose levels over time [19]. Noteworthy, although postprandial peak glucose levels were significantly higher for the soy-based formula, it did not meet the criteria for hyperglycemia.
Despite the increase in peak glucose levels following the consumption of a soy protein-based formula, the maximum increase in insulin levels was similar for all tested formulas. The fact that we only had three insulin measurements throughout the two-hour period in each session, as opposed to seven glucose tests, may have reduced accuracy in the assessment of the insulin response.
Lactose is the principal carbohydrate in breast milk, and its many benefits are well known. For example, it enhances calcium absorption (thus contributing to bone mineralization) as well as the absorption of other minerals, such as magnesium, zinc, and iron [26–28]. In addition, some of its derivatives and fermentation process products have a prebiotic potential, and are utilized by the gut bacteria from probiotic strains thus encouraging their growth. Furthermore, galactose, a monosaccharide that is one component of lactose, plays an important role in the brain and nervous system development, and is a vital source of energy for the brain, especially in neonates [29–31]. Therefore, regardless of its glycemic index, the removal of lactose from the infant's diet should be carefully considered if done without a compelling medical cause.
The soy protein-based formula is medically recommended for infants suffering from galactosemia (a rare hereditary metabolic disorder) or lactase deficiency (hereditary or acquired). However, it is otherwise not recommended for use during the first 6 months of life [32]. Soy is recognized as being one of the richest sources of phytoestrogens, which are plant ingredients similar in composition to mammalian estrogens [33, 34]. In addition, soy products are relatively rich in phytate, which binds calcium and impairs its absorption, and a soy-based formula contains significantly more aluminum than other formulas [35, 36]. Our present study may rise another reason to refrain from using a soy protein-based formula without justified medical indication.
The main limitation of our study is that the participants were adults and not infants who are the formula consumers and the research target. Unfortunately, this is unavoidable due to obvious ethical and practical reasons. We are well aware of the differences between the metabolism of infants and that of adults and the age-related differences in the enzymatic activity in the digestive system, which can affect the glycemic and insulinemic responses. However, it is reasonable to assume that infant will respond to these various formulas in a similar manner, if not in a more pronounced way. Another limitation lies in the assessment of the insulinemic response; its accuracy may have been hampered by budgetary constraint, because only 3 insulin tests per participant in each session were performed. A major strength of this study is that each subject served as his/her own control for the evaluation of each formula.
In conclusion, the hypothesis that formulas containing carbohydrate or protein substitutes would have different glycemic indexes than a typical formula was not supported by this study. Instead, this current study revealed a significant increase in blood glucose levels after consumption of soy protein-based formula when compared to standard and lactose-free formulas. The implication and clinical significance of these results have yet to be determined; however, we believe that these findings are of concern in the decision making process for pediatricians considering endorsing a soy protein-based formula without specific medical justification.