There is some evidence that whey hydrolysate formula can improve infantile colic, and limited evidence that casein hydrolysate formula may improve infantile colic. Studies of soya formula also suggest some benefit, but are of even poorer methodological quality.

• Whey hydrolysate formula:
• One randomized double-blind study of whey hydrolysate formula in 43 infants reduced crying by 101 minutes per day compared with control formula (95% CI 24 to 179 minutes) [Lucassen et al, 2000]. However, the authors reported that the blinding may not have remained concealed because of differences in the smell and colour of the two formulae, and differences in stools passed.
• A more recent randomized controlled study of 267 infants compared a new infant formula (containing hydrolysed whey proteins and prebiotic oligosaccharides, with a high beta-palmitic acid content) to a standard formula with simeticone [Savino et al, 2006]. Analysis of the 199 infants who completed the study found that infants receiving the whey-based formula had fewer episodes of colic (3.32 +/– 2.06) than those receiving standard formula with simeticone (1.76 +/– 1.60) (p < 0.0001; CI –1.0 to –2.1).
• Casein hydrolysate formula:
• One randomized controlled trial of 122 infants comparing hypoallergenic diet (casein hydrolysate formula or maternal hypoallergenic diet [free of milk, eggs, wheat, and nut products]) with control diet (standard formula or usual maternal diet) [Hill et al, 1995], found that the hypoallergenic diet reduced infant distress: 61% of babies receiving a hypoallergenic diet (33 out of 54) had reductions in distress (as measured by parents on a validated chart) compared with 43% (26 out of 61) receiving the control diet (odds ratio 2.12; 95% CI 1.00 to 4.46; p = 0.047). However, results for both bottle-fed and breastfed infants were pooled together for analysis by hypoallergenic diet or control in this study, limiting its usefulness.
• Evidence on the effectiveness of casein hydrolysate from crossover studies [Forsyth, 1989; Jakobsson et al, 2000] has not been included because infantile colic improves spontaneously over time, limiting the usefulness of a crossover design.
• Soya formula:
• One randomized study of soy formula in 19 infants also showed some benefit compared with cow's milk formula [Campbell, 1989]. However, other authors have questioned the adequacy of the double-blinding in this study [Garrison and Christakis, 2000].
• Infant soya milk is not recommended in the UK because of concerns that the phytoestrogen content may pose a risk to future fertility and sexual development [Committee on Toxicity, 2003; CMO, 2004].