Immune response to nucleotide-supplemented infant formulae: systematic review and meta-analysis

Abstract

Human milk is recommended as the only alimentary source for the first six months of life. Additionally there is a medical and social need for safe and effective alternative forms of nutrition for infants who cannot be fed with breast milk. Recently the safety and efficacy of some ingredients in infant formulae, such as nucleotides have been discussed. This systematic review analyzed the available evidence to establish the efficacy, safety and dose-response effect of ribonucleotide-supplemented infant formulae (RSIFs). Randomised controlled clinical trials (RCTs) comparing RSIFs to formulae without nucleotides or breast milk were considered in this review. Outcome measures were: antibody titres to common paediatric vaccinations, total lymphocytes, lymphocyte subclasses and NK-cells, episodes of diarrhoea and acute respiratory infection. Publication quality was determined using Jadad and CONSORT guidelines. Results were combined using a random effects model and reported through standardised mean differences (WMD) or risk ratio (RR). Systematic review and meta-analysis showed that RSIFs were associated with a better antibody response to immunisation with Haemopillus influenzae vaccine [SMD 1·74 (99 %CI 1·43 -2·05),, and fewer episodes of diarrhoea [RR 0·67 (0·58 -0·76), P ¼ 0·02]. We did not find a major risk of upper respiratory infections [RR 1·11 (0·90 -1·36), P ¼ 0·50]. Available evidence suggests a positive benefit of RSFIs on infant health without any risk. These benefits begin with nucleotide addition of 1·9 mg/418·4 kJ and are maintained or increased with 10·78 mg/418·4 kJ.

Dietary nucleotide improves markers of immune response to strenuous exercise under a cold environment

“…Exposure to cold environments has been claimed to elicit a stress response impacting immune cell function [10], but evidences from controlled studies are also scarce [13]. Research on the potential for dietary nucleotides to enhance the human immune response is wide but human trials are mainly restricted to critically ill patients [34] and to supplementation of infant formula [35]. To our knowledge, this is the first controlled study in which the efficacy of nucleotide supplementation has been evaluated in healthy individuals under multiple stressors such as strenuous exercise and cold environment.…”

Compositional Requirements of Follow-Up Formula for Use in Infancy: Recommendations of an International Expert Group Coordinated by the Early Nutrition Academy

“…The addition of nucleotides to formulae for infants has been associated with proposed benefits of immune and antibody responses to vaccination, protection against diarrhoea, benefits for gut microbiota composition, and infant growth promotion [86,87,88,89]. Nucleotide concentrations in formula ranging from 1.9 to 10.8 mg/100 kcal have been evaluated [88].…”

“…Nucleotide concentrations in formula ranging from 1.9 to 10.8 mg/100 kcal have been evaluated [88]. Older infants that consume FUF are also exposed to nucleotide supplies from a variety of complementary foods and are considered less sensitive to conceivable untoward effects than neonates are.…”

Metabiotics and their Health Benefits

“…Nucleotides have beneficial effects on early infant growth (Singhal et al, 2010), small intestinal growth and development (Rodriguez-Serrano et al, 2010), intestinal microflora and immune function (Hawkes et al, 2006;Gutierrez-Castrellon et al, 2007). DNA vaccines have been used to prevent allergic response (Horner et al, 2001).…”